Entries in brain (10)


Crossing the Blood-Brain Barrier: Done with all the guesswork?

Most researchers who study molecules in the brain, that are not already there, know the difficulty of penetrating the blood-brain barrier. The “BBB” is a tightly joined layer of cells that shields the inside of the central nervous system from harmful pathogens and toxins, by acting like a filter between CSF and blood. The problem is that this filter doesn’t know when doctors are actively trying to reach the brain with medication, for example to treat glioblastoma, Alzheimer’s or psychiatric diseases. Much research has gone into predicting whether a compound will make it through the barrier or not, but even today it is a lot like gambling to find the right molecule to reach the brain.

It is hard enough to cure brain cancer per se, but the additional burden of crossing the BBB makes treatment a fight against windmills. Now researchers in Toronto may have found a way to solve that problem: Using ultrasound, micro-sized gas bubbles in a patient’s blood can be set into vibration, very gently and only transiently disrupting the blood brain barrier. By doing so, for a short amount of time molecules that usually do not reach our brain are admitted to the usually so well protected part of our body. The use of this technique to deliver chemotherapeutics to glioblastoma is currently under investigation. However, not the entire blood-brain barrier is being disrupted: Highly specialized MRI equipment enable localization of the area, where BBB disruption would lead to a maximal delivery of the agent. Using super-focused ultrasound, researchers are then able to localize the area of BBB disruption with very high precision. Careful optimization of irradiation energy ensures reversibility of the process.

The latest in vivo result will show how effective the approach is, and if there’s promise for more broadly applicable versions thereof in the future. In any case, the creativity and interdisciplinarity makes me feel optimistic that we will eventually find ways to deal with the body’s toughest border, which would be a milestone towards understanding the brain and battling its diseases.


More about the topic:

The Toronto case: http://www.popsci.com/bubbles-burst-blood-brain-barrier-beneficial-or-bad

How it works: http://www.jove.com/video/3555/mri-guided-disruption-blood-brain-barrier-using-transcranial-focused

On the science behind it: http://link.springer.com/chapter/10.1007/7355_2013_37?no-access=true


The next five minutes could really help: Resting state fMRI predicts antipsychotic treatment response 

In Friday’s online issue of The American Journal of Psychiatry, Dr. Deepak Sarpal and colleagues published a ground-breaking new report where antipsychotic treatment response could be predicted using resting state fMRI.

Resting state function magnetic resonance imaging, or rs-fMRI for short, is a technique where changes in blood flow can be measured in the brain and plotted on the basis that increased blood flow means increased brain activity (and less blood flow means lower brain activity).  This method can reveal single hotspots (or coldspots) of activity, but with very high time resolution, can be used to identify how different regions of the brain are connected.  Using an identified hotspot as a ‘seed,’ fMRI analysis allows a mapping of when and where other changes happen in the brain during the resting period to create a network of functional connectivity.

Beginning with a ‘discovery’ cohort, Sarpal and colleagues found that in first-episode schizophrenia patients, analysis of a 5-minute rs-fMRI scan revealed that those who would later showed a lasting response to antipsychotic drug treatment (risperidone or aripiprazole) had lower connectivity stemming from the striatum.  The striatum is a region in the middle of the brain and, as a central part of the brain’s reward system, is known to have dysregulated function in schizophrenia. The current study found the striatum to be integrating measureable signals with 91 other functional connections.

By setting a threshold level of striatal connectivity, the authors found significant predictive power of their system in testing rs-fMRI data from a matched but independent ‘generalizability’ cohort of patients who were treated for an acute psychotic episode. Again, those patients who would go on to respond from antipsychotic therapy had subthreshold levels of striatal connectivity prior to intervention. 

A major step forward from this paper is identifying patients where treatment is likely to work – and at the same time, highlighting those patients who are likely to be treatment non-responders.

A key aspect of the work in our lab is in understanding the molecular changes associated with the normal and diseased brain. Using dual-modality imaging, we design experiments that can link fMRI with PET imaging to visualize specific molecules and enable understanding of how the regional density of a receptor/protein target relates to functional changes in blood flow. The recent findings by Dr. Sarpal et al could quickly open new doors to highlight what divides patient groups; by applying novel PET tools, we are poised to advance understanding of underlying protein targets could be exploited in next-generation therapeutics.


Sarpal DK, et al “Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment” American Journal of Psychiatry, Aug. 28, 2015.

AJP in Advance (doi: 10.1176/appi.ajp.2015.14121571).


Board games and your brain!

While looking up some strategies for a deck-building game called Dominion I happened to stumble upon a report on a forum discussing the benefits of board games on the prevention of cognitive decline. There are studies that show having a healthy diet, engaging in physical activities, engaging in social interactions, and performing mentally stimulating activities aid in prevention. In “A functional MRI study of high-level cognition. I. The game of chess” researchers used fMRI to identify the regions in the brain stimulated from the formation of strategies for playing Chess and GO. It was found that Chess mostly utilizes the left hemisphere while GO mostly utilizes the right hemisphere. This shows that games where there are new strategies and skills to be learned are mentally stimulating to keep the brain active. Another benefit for preventing cognitive decline while playing board games is the social interaction that provides mental stimulation. So play some boards games to have fun and prevent cognitive decline!

Deck-building:          Strategic games:                  Cooperative against the board:

Dominion                  Settlers of Catan                  Pandemic

7 Wonders                 Puerto Rico                           Shadows Over Camelot

Munchkins                Ticket to Ride                        Forbidden Island/Forbidden Desert

Ascension                 Small World





Can Dancing Improve your Ability to Remember?


A few weeks ago I was on the Green line heading to North Station when I realized that a young woman a few seats away was carrying a pair of tap shoes. My dance background is quite strong, but I haven’t put on my tap shoes in three years. I first started dancing at age three when my mom, some-what frustrated with my high-energy antics, signed me up as a way to tire me out. When I was packing for my summer in Boston, I brought my tap shoes because I knew I wanted to get back into it.

Long story short, I stopped this woman after we got off the train. She recommended a studio for me to look up, and I have been going to tap class once a week ever since.

What surprised me the most about getting back into my shoes was my ability recall dances that I have not seen or performed in years. My dance memory is far better and more accurate than most of my memory. I can even recall dances that I learned for the first time over a decade ago.

Upon investigating the connection between dancers and good long-term memory, I wanted to know what happened in the brain in response to high-intensity dance training and if there were changes in way new long term memories are created or stored. I found that studies have shown that dancers are able to use mental imagery better and with higher reproducibility than non-dancers even in laboratory settings (Blasing et al., 2012). Many areas of the brain are activated during motor learning, included many overlapping areas which could improve devoted concentration and therefore is thought to create a stronger memory. In a case-study, dancers were able to recall dances learned from over three years previously (Steven et al., 2010). The brain function behind long-term kinestetic sequence memory (dance is considered a sequence of steps) is currently not known and is difficult to study. Most studies have focused on ways to disrupt this long-term memory and have not been designed to determine how the disruptions are occurring in the brain, perhaps due to limited tools to study the brains of humans till relatively recently.

Scientists have used both fMRI and PET to study the brains of dancers, but it doesn’t appear that there is much current study using these techniques on long-term dancer memory. Typically, subjects have to remain as still as possible in the large scanners required for these studies. However, a group recently found a way to let ballroom dancers move through the steps with their feet on an inclined apparatus while lying in a PET scan (Blasing et al., 2012). They were able to see activated regions of the brain which were exclusively associated with dancing. This could open the door to more kinesthetic memory based studies using PET and fMRI.


For more information on what we do know about the brain and dance see: Nerurocognitive Control in Dance Perception and Performance (Blasing et al., 2012)

For more information on dance and long-term memory see: Backwards and Forwards in Space and Time: Recalling Dance Movement from Long-Term Memory (Steven et al., 2010)




Street view for the Brain: mapping the connectome

The race to understand the human brain is vaguely reminiscent of that to map the human genome 10 years ago. Since last year’s presidential announcement of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, there seems to be an omnipresent interest in understanding the complexities of the mind. Similar to the human genome project, there is a major effort to demystify the brain by creating a map of the underlying connections and circuitry—the connectome. A clear reference picture of how things look and work when they are functioning properly in a healthy human brain affords the ability to identify differences that arise with damage and disease. Although this may sound like a straightforward task, you must consider the number of variables involved: mapping 80+ billion neurons, 10,000+ neural connections, throughout each stage of development, learning and aging - it is an image of a dynamic process. Here at the Martinos center, scientists are hammering away at the human connectome using various MR-based imaging tools like diffusion tractography, which traces axonal fiber bundles throughout the brain indicating the path connecting functionally-related regions.

Animal models offer the advantage of manipulability and permit much more invasive techniques, which scientists are using to create a “mesoscale” connectome map. Researchers at USC (www.mouseconnectome.org) and the Allen Brain Institute (www.brain-map.org) are creating atlases of individual axonal projections by injecting anterograde/retrograde tracers and fluorescent protein producing virus, respectively, directly into specific brain regions. By following the path of the tracer or the virus, they can define the network of potential connections each neuron can make within the brain. Both of these projects take a systematic approach, breaking the brain down into a navigable, albeit massive, data sets. The best part being that these data are publically available online for use by other scientists- or for anyone to peruse! Both of these studies were recently published and will surely serve as an invaluable resource during continued efforts to understand the brain and learn to repair damages to it.


a, The data generation and processing pipeline. QC, quality control. b, The two main steps of informatics data processing: registration of each image series to a 3D template (upper panels) and segmentation of fluorescent signal from background (lower panels). c, Distribution of injection sites across the brain. The volume of the injection was calculated and represented as a sphere. Locations of all these injection spheres are superimposed together (left panel). Mean injection volumes ( ± s.e.m.) across major brain subdivisions are shown (Image from Oh et al, 2014)


SW Oh et al. “A mesoscale connectome of the mouse brain,” Nature, 000, 1-8, 2014. 



B. Zingg et al., “Neural networks of the mouse neocortex,” Cell, 156:1096–1111, 2014.


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