Sunday, January 11, 2015

Smart phone use changes the brain

One of the most remarkable things about our brains is how organized they are. Sensory information from our eyes, mouth, skin, nose and ears goes to different locations in the brain. For example, visual signals are processed first in the very back of the brain, whereas sensations of touch and pain activate the middle region of the brain called the somatosensory cortex.

Functional organization of brain cortex. (Source:
Remarkably, the brain gets even more organized from there. Within the visual cortex, there are columns of neurons that only respond to light that is horizontal and others that only respond to lines that are tilted 45 degrees. The somatosensory cortex is also highly organized, with different parts of the body represented by specific sets of neurons. If you were to send electrical shocks into one specific area of the somatosensory cortex to activate those neurons, you may elicit feelings of touch from the right thumb, even though the subject is not being touched at all. Move those electrical signals over slightly to another area, and the subject may feel touch instead coming from the palm of their hand.

Wow, right? But here’s the real mind blower: this organization can change over time as the person experiences different sensory inputs. If you are a violin player, you feel the strings with your fingertips a lot, so the fingertip part of the somatosensory cortex is super active. This extra activity allows the fingertip representation in the brain to grow and recruit nearby neurons to also respond to touch in the fingertips. The cortical representations are “plastic” and always changing with use.

A violin player may practice this one particular skill a lot, but what about other activities we do everyday with less intensity, like using smart phones? Think about how often you are swiping the screen with your thumb. That’s a lot of sensory information being sent to the thumb part of your somatosensory cortex. Would this increase the thumb representation in your brain? A recent paper by Gindrat et al. addressed this exact question using EEG to record brain activity in smart phone users versus people with the old-style cell phones.

How can you actually measure the area of body representations in the somatosensory cortex? You could stick electrodes into people’s brains and record the activity in their neurons, but that’s a little invasive. You could put them into a MRI machine and measure brain activity when you touch their thumbs, but that is time consuming for so many subjects (37 total). Instead, the authors used a method known as electroencephalography, or EEG, which consists of 62 surface electrodes placed on the scalps of the subjects. Each electrode records the summed electrical activity from all the neurons positioned right under the electrode. Before an experiment, all the electrodes would be picking up a baseline of activity from lots of different neurons firing asynchronously. However, during an experiment, there is a single stimulus (like touching the subject’s thumb), which elicits activity in a lot of neurons all at the same time. This activity summates to give one large response called the event related potential (ERP), which is recorded by the nearest electrodes.

EEG electrodes record brain activity (source: Wikimedia commons)
Finger representations in smart phone users
The ERPs for the thumb, index finger and middle finger were larger for the smart phone users than for the non-touchscreen users. There was a correlation between the amount of phone use per hour and the ERP, so the more use, the greater the ERP, which is to say the more activity in the somatosensory cortex. The number of electrodes recording the ERP was greater in the touchscreen users, so when you touch the thumb of a touchscreen user, a larger part of the somatosensory cortex responds. In other words, the thumb representation was larger in smartphone users who use their thumbs more often.

The more recently the subjects had used their phones intensely, the larger the ERP for the thumb, which indicates that brain remodeling occurs on a very short time scale (within 10 days in this experiment). Interestingly, there was no correlation between ERPs and the age at which the subject started using a touchscreen. This is in contrast to the previous experiments done with trained violin players, which did show a correlation between the size of the finger representations and the age at which they first started playing. The authors suspect that a trained violinist develops a more stable sensory representation than touchscreen users who are casually using their phones (as opposed to years of disciplined practice).

So the take-home message is that normal day-to-day activities can influence brain plasticity and the way our sensory representations are organized in our brains. This could be a good thing, because subjects develop better touchscreen skills. On the other hand, the enlarged thumb representation could cause focal dystonia, which is characterized by involuntary muscle contractions and sometimes pain, as the various body part representations lose their distinct boundaries and start to overlap. This probably won’t be a problem for most phone users, but be forewarned all you smart phone addicts out there.

Monday, January 5, 2015

What big nuclei you have!

Eggs get ready for fertilization by producing and storing all the proteins necessary for early embryo development.  After fertilization, there are a series of rapid cell divisions without growth, producing a lot of small cells (here's a video).  At some point during this process, the embryo switches over from using the proteins from mom, to expressing their genome to make their own proteins.  This transition to embryonic transcription is known as the midblastula transition, or MBT.  How does the embryo know when it is time to turn on gene expression? 

One theory is that the ratio of nuclear to cytoplasmic volume (N/C volume) is the trigger for MBT.  The nucleus is where DNA is stored within a cell; this is where gene expression occurs.  The cytoplasm is the goo that the nucleus sits in.  During those rapid early cell divisions, nucleus size does not change much, while the cytoplasm in each cell keeps getting smaller and smaller.  The N/C volume increases, since the cytoplasmic volume is decreasing.  Is there a certain threshold of N/C volume, above which the embryo switches on gene expression?

Jevtic and Levy did a series of clever experiments, using frog embryos to address this question, which was published today in Current Biology.  In Xenopus laevis frogs, the midblastula transition always occurs after the 12th cell division.  The researchers manipulated the nucleus size in the frog embryos to see if that would change the timing of MBT.

Changing nuclear volume
The authors were able to increase nucleus volume by injecting embryos with mRNA for importin and a type of lamin.  Importin acts as a shuttle that brings other proteins into the nucleus, including structural proteins that make up the nuclear envelope.  Lamins form the inside of the nuclear envelope, so by injecting the mRNA for these two proteins, they caused overexpression of nuclear proteins that will make the nucleus grow larger.  To decrease nuclear size, they instead injected mRNA for a protein that causes another cell structure to grow (the ER) at the expense of the nucleus.

They injected the mRNAs and a red dye into one cell in the two-cell stage.  When this cell divides, its daughter cells inherit the red dye and the mRNAs and proteins that change the nucleus size.  Thus, by the time a normal embryo is ready to undergo MBT (the midblastula transition to express their own genes), half of it will be red and have abnormally sized nuclei and the other half will be normal and act as an internal control. 

N/C volume triggers MBT
They looked at embryonic gene expression (as a readout of MBT) in the cells with abnormal nuclei at different developmental stages.  The cells that had larger nuclei reached the critical nucleus to cytoplasm (N/C) ratio earlier in development and began expressing embryonic genes earlier than the neighboring cells with normal nuclei.  Likewise, the cells with smaller nuclei took a little bit longer than normal to undergo MBT.  I love that the two halves of the embryo are out of sync with each other just because the sizes of the nuclei are different.  This really shows that there is a critical N/C volume and manipulating this ratio is sufficient to initiate the midblastula transition.  

How do the cells know the size of the nucleus and cytoplasm?  The authors suggest that the oocyte must have inhibitors in it that repress transcription, so the embryo’s genome is inhibited at first.  As the cells divide, these inhibitors are split among them, so the inhibitors become less and less concentrated in each cell.  Once they reach a certain low concentration, they no longer function, so the cells can begin transcription.  This would explain why increasing nucleus size would cause an earlier midblastula transition: the larger nuclear volume essentially dilutes the inhibitor further, so it reaches that low threshold concentration sooner.  It’s important to get the timing of gene expression just right during development and the N/C volume appears to be one way that cells manage to do this.