Tag Archives: Brain

Let There Be Light! A breakthrough in microtechnology that is giving blind people back some sight.

I couldn’t imagine loosing any of my senses, least of all my sight. To go blind slowly over time must be one of the most challenging illnesses a person can have to face. Knowing that there is nothing that can stop a hereditary degeneration of your sight must be heartbreaking, to say the least. Just imagine having the memory of what a flower covered in morning dew looked like as a sunbeam touched the tip of the petal, or being able to recall how you used to look in a mirror but can no longer see yourself, to know that there are wonders beyond most peoples own imaginations that are possible to observe in a sunset and to have all of that knowledge, that discover, taken from you along with your independence has to be one of life’s most unfair consequences of genetic illnesses.

Like any disability that worsens over time you’d hold on to the hope that one day science will find a cure, but it would seem an unfathomable wish for them to cure blindness. This is why the news that came out this week of a microchip that has the potential to restore at least the basic functions of sight seems almost too good to be true.

Some forms of blindness are caused by a degeneration of the photo-receptors within the eye. These are the cells that allow us to interpret light signals into meaning, by building on signals received about colour and brightness. With this information our brain is then able to construct the images that allow us to perceive the world around us. Clever, clever nature.

In people with degenerative eye conditions such as retinitis pigmentosa (RP) the optic nerve is left mostly intact. There are two ‘treatment’ options available at the moment, the first involves forms of gene therapy and other protective factors, which have been shown to slow degeneration in people with this and similar conditions. However, this has to be received at an early enough stage of the degeneration.  The second option is what this current research focused on, and sounds more like something from a science fiction film than reality. They invoke electrical stimulation of the surviving retinal networks to try to produce some form of visual experience in people who’s level of degeneration is beyond that which might be helped by the other form of ‘treatment’. More specifically in this case a microchip is implanted under the transparent retina to act as electronic man-made ‘replacement’ photoreceptors.

The chips are able to sense light and create signals from this at many pixel locations. This is achieved using “microphotodiode arrays” or MPDA’s.  There are 1500 pixel generating arrays on a chip, and each acts independently as a light sensitive electrode, this is subsequently able to provide an electrical stimulus to the neurons nearby. In this way it is unique to other approaches, within each element is the electrode set allowing for the electrical stimulation of neurons to be caused by the reception of light. There are also photodiodes found within the chip which allow for varied amplifications to be transmitted based on the level of light reception.

With the chip in place within the eye, the photodiodes are able to capture an image each, several times a second, simultaneously.

Illustration from the original paper found here . It gives a better demonstration of the set up of the microchip with the electrodes and MPDAs, and also a nice picture of an eye is always a winner. (I can remember dissecting an eye in alevel bio, it was fascinating)

It’s enough to make your head hurt to think about, I mean really. There are 1500 elements able to transmit signals from the photodiodes, which are able to capture an image in a ridiculously small time frame and transfer this into meaningful information by way of electrical impulses to the bipolar cells that would have originally received information from the rods and cones of the eye. With the amount of current that is sent by each electrode determinable by the brightness recorded by each photodiode.  Oh, did I also forget to mention that the chip that all of this occurs on is a mere 4mm square in size!

In this trial study of ‘the chip’ three people with hereditary degenerative blindness were given the implant. They were tested 7 to 9 days after the implant with some psycho-physical tests. If they achieved well on these they went on to be tested for recognition of everyday objects. Due to the electrical nature of the chip it was possible for two test conditions to be employed for all these tests, a chip ‘on’ and chip ‘off’ baseline condition, which allowed for statistically significant results to be acquired.

All three patients were able to detect single electrode single pulse simulations, the perception of this varied slightly between patients but they all reported seeing the stimuli.

They went on to distinguish letters from one another, patient one begin able to tell the difference between U and I, and patient three going further by successfully distinguish four letters presented at random. Patients were also tested on pattern recognition, two of the three were able to correctly distinguish the direction of grid patterns, showing that the chips have high spatial resolution capacities.

Patient two show better recognition in further tests, and interestingly was the only patient of the three to have the chip placed in a slightly different part of the eye. In these cases the patient, identified as Miikka, was able to name objects presented in an unknown dining table situation, including distinguishing between a fork and spoon, as well as an apple and banana.  In subsequent optional tests he went on to read his name (a clip that many will have seen on the news) and pointed out the fact that they’d made a spelling mistake!

The fact that they’d only had the chips in place for just over a week and this was having an impact on their perception of light is impressive enough, but for one participant to go on to read their own name is quite incredible for a first trial.

It’s difficult to find fault in this study, you could say it only worked very successful on one subject, but that wouldn’t be fair at all. It seems promising that all of the patients were able to respond to light stimuli in the first instances.  There are any number of individual differences that might account for the relative different levels of impact that the chip had on all three participants.  One might try to say the media exaggerated the findings in some way but the majority of the reports I saw were very careful to give a full background of the type of blindness that this is appropriate for, as well as the fact that it is very new technology and that it doesn’t ‘restore full sight’.

No questioning then that the results are truly remarkable, and although the success wasn’t replicated in all three subjects, all involved had slight improvements above the level of vision that they had previous to the implant. This research is clearly going to continue to develop into something more and more complex throughout its research future and I hope it can go on to be offered to people with RP more widely in years to come.

It is not often that there is a developement of such magnitude that I’d feel comfortable ending on such a hopeful and positive note but I really do think that this will one day be able to improve the everyday lives of those who have degenerative eye sight. I hope that it’ll go on to allow them to regain the independence that has been taken from them by their conditions and also relieving some of the demands on the carers who have to become their replacement eyes at the moment.

The original paper is:

Subretinal electronic chips allow blind patients to read letters and combine them to words

Eberhart Zrenner, Karl Ulrich Bartz-Schmidt, Heval Benav, Dorothea Besch, Anna Bruckmann, Veit-Peter Gabel, Florian Gekeler, Udo Greppmaier, Alex Harscher, Steffen Kibbel, Johannes Koch, Akos Kusnyerik, Tobias Peters, Katarina Stingl, Helmut Sachs, Alfred Stett, Peter Szurman, Barbara Wilhelm, Robert Wilke.

and a full free PDF can be found here !

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Update: Apparent symptoms of neglect in Barley

It’s difficult for me to write with 100% accuracy about her progress as I am at university 80 miles away from home so am relying on interpretations from emails/photographs and updates via the phone from my mom (who is being incredibly helpful, so big thanks is due!).

But Barley’s most recent progress seems quite promising. My mom said she’d noticed Barley’s ‘fussy eating’ (as she calls it) about 2/3 weeks ago after what was likely to have been another stroke since her first major stroke just over a month ago, which left her with a strong left side weakness which she is now recovering from. The photo’s she has sent today indicate that if she is showing  signs of neglect or another similar neurological condition that these  symptoms are beginning to subside. However, I still think that they way in which she is eating is still very interesting, see the below photos for an illustration.

There seems to be a definite right side preference for the food bowl, (image one) and she clears a whole half almost down a straight line bisection before she moves across to the second ‘half’ of the bowl on her left hand side (image 3). The fourth picture seems to indicate she has changed position slightly, as in the previous photos she is standing right in front of the bowl and in this image she seems to be at it’s side. Again I’ll stress that I do not know precisely how she is eating, I keep trying to get my mom to work out video on her photo so we can have a more accurate step by step portrayal of this.

The fact that she’s managing now to eat her entire bowl without promting is a nice postive sign, I suppose as cool as it is that she’s showing these signs of a neglect I do really want her to get better and make a good recovery. I’m not all about ‘the science’.

I’ll end with this image of Barley being looked after by our new Puppy called Moya (who’s in training to be a dog for the disabled for my mom who has a degenerative spinal condition. I love Moya, she is awesome even if she ate my teddy bear last time I went home!)

Thanks to all of you who’ve seen the post about Barley and have shared it around. If anyone has any suggestions as to how I might better test for neglect signs other than with her food bowl please don’t hesitate to put them forward! I’m also not sure how long neglect can last in a dog when it hasn’t been induced medically for scientific research purposes. So I’d be most grateful for any info from those with veterinary science backgrounds or experience with such things as well. All other information about this condition that anyone may have would be really great to see too!


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fMRI is not a ‘Brain Telescope’, yet.

The telescope was and continues to be one of the most important inventions in the study of astronomy, it led to the discovery and understanding of our entire solar system and continues to add to our knowledge of the universe!  This is because it is understood, and the methods used in the application of the telescope are designed to further our knowledge to the best of its ability. It improves over time, and in doing so allows our knowledge and understanding of some of the most unfathomable ideas about our universe to improve also. Neuroscience is not lucky enough to have a brain telescope, and the most used method of investigation in current times fMRI is far from comparable to the telescope, if anything it is more like a kaleidoscope.

Great basis for a research tool, not fully understanding it’s connection to what the ‘activity’ shown is interpret reflect and what is actually being recorded.  I suppose this is why some people call fMRI ‘the new phrenology‘?

fMRI could be equated to using a hammer to put a screw in the wall, sort of does the job but it doesn’t have much of a hold once it’s in there. There must be a better analogy out there but I just can’t think of it, perhaps it’s because if someone else or another scientific field tried to apply the same certainty to the results of a method it was using without fully understanding it they’d be laughed at. It can’t be all bad though surely, otherwise we wouldn’t be using this incredible machine for such rigorous academic investigations?

So I reckon that the general opinion people have of fMRI data is that a brightly coloured area on the brain shows an increase in some unqualified sort of ‘activity’. In fact this is exactly how it’s often reported in published (and therefore peer-reviewed) articles. It’s not just the lay persons or the humble students view, that the ‘areas that light up’ in these scans are meant to be showing which brain areas are involved in what ever process is being studied, but its more surprising that often in published work this assumption is taken for granted. What do I mean? Well yes, good question, let me explain.

Firstly, I should say that what those ‘coloured’ images are actually showing is something call the BOLD signal. This is the blood oxygen level dependent signal. It reflects changes in blood oxygen levels in particular brain regions. This is important to remember because seeing blood oxygen levels change in one area is not the same as seeing neural activity in that area. An important fact often ignored.

Not wanting to get too scientific about this, but not having much choice, what we need to consider is something called ‘neurovascular coupling‘. This refers to how neural activity relates to respiration. Neural activation of any kind requires energy, this energy comes primarily from glucose carried in cerebral blood flow, though it has been suggested that other substances such as glutamate, lactate and glutamine as well as some others, may also be oxidised by neurons (Zielke et al., 2007 in Mangia et al, 2009). Many studies have been conducted using laboratory animals that show a conclusive link between glucose consumption and localised neural activity, though the distribution of that energy consumption is far less straight forward amongst individual neural mechanisms. A study on the brains of rodents suggest that the majority of energy, up to 34% of all being used, is actually used in postsynaptic excitatory neural responses as opposed to an even distribution of  resources involving presynaptic responses, synaptic terminals and maintaining the resting potentials of the cells. In humans this proportional distribution of energy for postsynaptic events could be as high as 74% (Attwell & Laughlin, 2001). It could be that the BOLD signal is therefore most correlated to postsynaptic activity within the brain.

Sounds nice and convincing right? Well no, cause it’s also been suggested that BOLD signal might be showing presynaptic activity, particularly in the glia cells which use vast amounts of energy consumption in their active state (Jueptner & Weiller, 1995). It might seem inconsequential to worry about which bit of neural activity fMRI is showing, the beginning or the end but this is of great importance for furthering our understanding of what is actually happening.

It is also worth remembering that there is a known delay in haemodynamic response to neural activity. That is it takes a while for blood to reach an area where energy is depleted and respiration needs to occur. One way of countering this is using a particular form of analysis when looking at the raw data. Methods such as Canonical Correlation Analysis (Friman et al. 2001) not only remove a lot of the noise from fMRI data samples but also takes into account haemodynamic response delay. Good huh?

I think that it is unfair to label fMRI the new phrenology, it is by far one of the most impressive inventions of recent times and has the potential to inform us about some of the mysteries surrounding what it is to be human and how our magnificent brains work. Give it time, like the telescope, it’s design and application just need to be improved, and this takes centuries.

One day it might just reveal to us the question that gives the answer to ‘the meaning of life, the universe and everything’, if Douglas Adams was correct.

I strongly believe that the best way forward for the moment, given the lack of understanding of mechanisms such as neurovascular coupling is that fMRI analysis continues but is treated with far more caution, and that perhaps combination methods such as MEG and fMRI, or EEG and fMRI might be able to provide more accurate results about the levels and areas of activity.

Don’t always trust those pretty pictures you see, just because they look nice.

P.s and while were at it can we just call MRI by its correct acronym?? NMRI.. that would be NUCLEAR magnetic resonance imaging.  Why do we pander to the concerns a simple and correct use of that word will have on public opinion?

This is science, deal with it.

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