A new way to study memory in Down Syndrome

Why Haven’t They Done That Yet?

This is a strange post because I am talking about someone having done the work I will write about, but I am asking someone to do the work. This is my way of trying to drum up replications and increased n’s. I think as scientists we need to replicate every finding we see in populations with developmental disorders, and then extend the research into different disorders to identify commonalities and differences among each disorder’s cognitive deficits.

Also, I feel it is necessary that we not only identify cognitive deficits in patient populations, but we also try to unpack the nature of these deficits. In other words, we try to understand how their brains work, not just ask if they perform worse than a control group.

This post is about some work from a former collaborator of mine as well as some work my old advisor did in an associated mouse model. Briefly, they showed that children and adolescents with Down Syndrome actually process the visual world differently than the rest of us in a very interesting way that has implications for intervention studies. I will also be asking why has this not been done before and is anyone going to follow up on this and test if the same phenomenon exists in other disorders.

I will talk about portions of the paper entitled Dentate gyrus mediates cognitive function in the Ts65Dn/DnJ mouse model of down syndrome that appeared in Hippocampus by Gen Smith et al. and the paper entitled Remembering things without context: Development matters that appeared in Child Development by Jamie Edgin et al.

What Should Be Studied and Why?

Smith and colleagues did a rather ingenious thing in their experimentations. They looked rather closely at the data they were collecting in the Ts65Dn mouse model of Down Syndrome. They ran a series of experiments and found out that they were seeing effects that made absolutely no sense given what we know about spatial memory and the brain. They were getting what appeared to be object recognition deficits that had to do with impaired dentate gyrus function. For those not in the field, this does not really happen. At least not that we know. Not in a normal brain at least.

Further experiments were required to figure this out and determine if the Down Syndrome brain is fundamentally different in this way.


In parallel, Edgin and colleagues were grappling a similar question in their research with individuals with Down Syndrome. They were seeing eerily similar effects that seemed to make no sense… And this mystery needed to be solved

A Valid Approach and Likely Interpretation

Independently and in parallel, both groups came to a very similar solution. Smith and colleagues proposed that there might be an effect of context influencing the object recognition. In other words, if you run a task wherein you ask a mouse to identify an object it matters if the box is clear or opaque. Let me explain. If you do a simple object recognition task in an opaque box, the Ts65Dn mice can do it, as can wildtype mice. However, if you use a clear box that lets the mouse see everything in the environment, they get confused and no longer can perform the task, but wildtype mice can. This suggests one of two things, 1) that the Ts65Dn mice are not able to focus on the object, but get distracted by the environment. or 2) The Ts65Dn mice actually fuse the object with the environment when in a clear box and it is just too complicated for them to process given they have a messed up dentate gyrus.


Edgin and colleagues have a similar solution as well as a similar interpretation. Edgin and colleagues tested kids with Down Syndrome across ages to see if there was a difference in the development of object in scene learning. In one condition they showed a scene and tested if the kids could remember a scene. In another condition there was an object in the scene and they tested if the kids could remember the object in the scene. the last condition showed an object in a scene, but tested if the kids could remember the object when the test did not include the scene.

What they found was that for the kids with Down Syndrome, there was a deficit for remembering scenes as well as a deficit for remembering an object if it was presented in a scene, but no deficit for just remembering an object. They interpreted this as evidence that kids with Down Syndrome perhaps are processing scenes and objects differently than typically developing kids.

So what do you propose?

What I propose needs to be done, and frankly it amazes me how rarely this line of contact is followed, is to evaluate exactly how developmental disorders change the way the brain processes stimuli. In other words, these two papers were great because they came up with a mechanism demonstrating that the Down Syndrome brain (and Ts65Dn brain) actually works differently than the typical brain. They did not stop at, “Hey look, there is an impairment, lets give them drug X”, they tried to determine the precise nature of the impairments. Were they impaired, as in cannot do it? Or were they impaired as in they do it in a different way that fails our particular test. In the case of object recognition, at least at short delays, it is actually clear that there is no real deficit related to Down Syndrome, the apparent deficit is due to task confounds that were not controlled in earlier experiments.

I hope this line of research continues. Long term, we are not going to be able to medicate every child and adult with every developmental disorder. We are going to have to get creative to design appropriate solutions and teach coping skills to individuals in these populations. Unfortunately, in the present translational research context, we are looking for a targetable outcome that can be used to test drugs. But…we are not taking the effort to actually quantify the differences. Once we understand the differences it becomes possible to design training regimens to help integrate individuals with developmental disorders into the job market, design video game or computerized interventions to help them overcome cognitive weaknesses, and perhaps leverage their cognitive strengths to compensate for their weaknesses.

However, we have to ask the questions and run the experiments before we can do all this. And not very many of us are. Nor does it appear we are going to start anytime soon.

Open Hardware/Software Leads to a Better Behavioral Tasks

Ooh Ooh Ooh! They Finally Did It!

So this has been a GREAT week in research. A new protocol was reported for building an open-hardware/open-software operant chamber for testing rats called the ArduiPod Box. Now I have been planning and scheming on how to do this for ages, but never got around to it. I have NEVER felt so grateful to be scooped in my entire life!

The manuscript discussed in this post is “ArduiPod Box: A low-cost and open-source Skinner box using an iPod Touch and an Arduino microcontroller” by Oskar Pineño from Hofstra University. It was published in Behavioral Research Methods. The author’s website where you can download the software is located Here

Special thanks to Jason Snyder for bringing this article to my attention!


An Innovative Approach

In his study, Oskar Pineño sought to solve an enormous problem plaguing behavioral neuroscience-that of having to spend at least <$7,500 USD/chamber on the equipment necessary to perform operant tasks. This is a problem since often to get grants you have to show that the task you plan to use works, but cannot afford to buy the equipment until you get a grant.

Instead of spending a lot of money on a commercial operant chamber, Pineño pursued an alternate path, he decided to combine already available technologies to make the equipment himself for under $500 USD. What excites me about this approach is that Pineño uses an iPod touch in combination with an open-source electronics platform called Arduino (Link) to accomplish the same research goals as a full operant chamber, but literally at under 1/10th the cost.

By making such research options accessible to small labs (for comparison it takes over $50,000 USD to set up a lab with 8 operant chambers for high throughput testing), this equipment may serve to stimulate a surge in behavioral research. Particularly, ther emay be a resurgence of research relating to learning theory and other quantitative psychology/biology research (for a resumé of such research I recommend a visit to the website of SQAB-the Society for the Quantitative Analysis of Behavior).

Any resurgence in this type of research is bound to lead to new hypotheses and perhaps some sort of quantum leap in the field. There has long been a movement away from operant conditioning in behavioral science, but I for one, feel that this may be reversed with the availability of relatively cheap behavioral apparatus. In fact, I am keen to get my hands on the components myself and see what questions I can answer with them.

Although the ArduiPod Box not as yet been used in mice as of yet, I harbor hope that this type of research will open the door to more sophisticated studies of learning and memory processes in mutant mouse models being used to study human disease. The iPod touch is easily sensitive enough, so it is a matter of patience and careful task development. Perhaps even direct analogues of computer based tasks such as the NIH Toolbox (Link) or Stroop-like tasks of attention (Link1, Link2) may be developed in the future.


An example of the equipment needed to build this chamber (except the plexiglass cage) is below (from Dr. Pineño’s Website):

Necessary Equipment

Clockwise from left: iPod touch, Bareduino 328 Plus board, Redpark Serial cable, servo motor, and Arduino Uno board


And a video of the equipment in action is below, from the same source:

This 5 min video demonstrates a rat performing a simple discrimination task using the ArduiPod Box (i.e., when the bottle retracts and screen goes blue, the rat has to touch it to be able to drink again)


In my mind this equipment is absolutely revolutionary. Earlier experiments by Kenneth Leising’s lab at TCU have used an iPad as the touchscreen in an operant chamber, but that setup required a commercial system to be purchased and retrofitted to accept the iPad Link. The methods reported by Pineño will allow researchers between grants or in teaching/community colleges to perform behavioral research that will further the field.


Conclusion

Overall, the ability to use something like an iPad touch in concert with some open hardware options opens up behavioral research using operant chambers to an entirely new group of researchers: specifically those at small colleges that must rely on small grants due to the nature of their research, as well as for educational purposes (e.g., Psychology classes may actually be able to use such equipment in lab courses to give hands on understanding of the research performed by BF Skinner).

In fact, Oskar Pineño put it best in his paper, the final paragraph reads as follows:

Certainly, the ArduiPod Box is not without problems (as is shown by the results of the experiment here reported), at least in its current version. However, as an open-source device, the ArduiPod Box could be tremendously transformed in a short time, as it is improved or even adapted and modified to fit new uses by a thriving community of developers and makers, some of whom also hold a passion for the science of animal learning and behavior. Moreover, this device could also encourage young researchers to adopt a DIY philosophy, thereby investing time and effort to create their own experimental apparatus. With time, we might once again experience technological innovation in our research field, a field that enjoyed its most fertile moments during the 20th century thanks in large part to the tradition initiated by B. F. Skinner, great scientist and ingenious DIY maker

I could not agree more.


As a bonus, here is a video of a frog playing Ant Crusher on an iPod touch