Music to my Ears?… Just Kidding

February 3rd, 2011 in News 0 comments

Bookmark and Share

It was an average Wednesday night at 8, and I was channel surfing. As I changed the channels I heard singing; I knew instantly that the show was American Idol.  Most of you watch or have watched the show in the past and time and time again it befuddles me to think how these individuals think that they can sing. Most of the singers not only have piercing voices, but they are off key and sound terrible. After most auditions, the contestants – although I know it was horrible – still believe their rendition of a Whitney Houston song was outstanding. If you are like me then you want to know why.

Tone-deaf individuals do not have brain damage or trouble hearing, and they are definitely not suffering from a lack of exposure to music.  So what actually makes people unable to understand their inability to sing? Researchers conducted an experiment that tested the connectivity of the arcuate fasciculus (AF), which connects the temporoparietal junction (the place where the temporal and parietal lobes meet), with the frontal cortex in the brain. This junction allows neural substrates of sound perception and production to be connected. The researchers hypothesized that there are structural and functional abnormalities that contribute to tone deafness.

To test their hypothesis, structural MRIs with diffusion tensor imaging (DTI) were performed on the patients. DTI is a type of MRI that allows researchers to map internal structures with the diffusion of water. After processing the information, the maps identified that the right superior AF was diminished compared to control, signifying that the AF is disrupted in tone-deaf individuals. Also, resultant fibers in tone-deaf individuals projected dorsally toward the parietal lobe and/or translocally to the left hemisphere and not toward the ipsilateral inferior frontal gyrus where normal individuals have projections.The imaging and testing of the AF led researchers to conclude that the superior branch is responsible for fine-grained discrimination, and the inferior branch is responsible for automatic matching of sound output to its target. They also tested the volume of the fibers connecting each part of the brain and discovered that tone-deaf individuals have a lower volume of fibers than the control, which is important for conscious pitch determination and the degree of action-perception mismatch. According to the experiment, both the superior and inferior branches of the AF are needed for accurate perception and production.

Brain imaging

Figure 1: A comparison between the regions of interest of the posterior superior temporal gyrus (pSTG) and the   posterior inferior frontal gyrus (pIFG) of the right side of the brain

Tone-deafness is a new disconnection syndrome that deals with impaired pitch perception and vocal sound projection. There are no known genes that are associated with this condition that affects the AF fibers and their connection between the superior and inferior areas of the brain. So for all of you non-tone-deaf American Idol viewers, you will just have to sit through the next episode and know that most of singers cannot help but obliviously sing off-key.

Other Reading of Interest:

Tone Deafness – Scientific American

The amusic brain – BRAIN: A Journal of Neurology

Tagged , ,

Lasers: The Key to Mind Control?

February 2nd, 2011 in News 2 comments

Bookmark and Share

The ColBeRT DMD (digital micromirror device)

As a neuroscientist, one typically becomes accustomed to thinking outside of the “box.” After all, the brain is incredibly complex and cryptic, and some creative thought is required to develop methods to uncover its secrets.

Francis Crick advised that the greatest hurdle standing in the way of neuroscience is the inability to specifically stimulate a single neuron without altering any of its surrounding cells. This daunting task appears to be a thing of fantasy when considering the innumerable intricate connections the brain is composed of. However, Harvard University’s Samuel Lab has made a reality out of a dream with their groundbreaking research involving transgenic C. elegans. Recently published in Nature, the research of Dr. Andrew M Leifer and his team utilizes a manipulatory optogentics technique called ColBeRT to control the nervous system of a worm with the light from a laser.

Optogenetics is the methodology of employing genetics and visible light to manipulate the activity of living cells. In order for optogenetics to be applicable in the laboratory, the insertion of opsin genes, which encode for light sensitive proteins, into an organism’s genome is necessary. The activity of the resulting opsin-containing cells can be regulated by exposure to visible light.  Relative to the work of Leifer et al., optogenetics provides a platform by which the genetically altered motor and sensory neurons of C. elegans can be controlled with the use of a precise laser. Why use C. elegans? According to Leifer et al., “the nematode C. elegans is particularly amenable to optogenetics owing to its optical transparency, compact nervous system and ease of genetic manipulation.”

ColBeRT schematic

A schematic of the ColBeRT technique

The ColBeRT (Controlling Locomotion and Behavior in Real-Time) technique, which was designed  for the optogenetics research being done at The Samuel Lab, provides a way to specifically track a worm’s movement. A video camera with real-time feedback follows an illuminated and moving C. elegans under a dark field. The worm is placed on a motorized stage, which keeps the image of the organism centered in the camera’s view. Once the worm’s movement is recognized and registered by a specialized graphical user interface (GUI) software called MindControl, the image of the C. elegans is processed and the worm’s image is divided into 100 evenly spaced segments. From these segmented portions, specific target cells can be chosen, the locations of which are transferred to a DMD (digital micromirror device). This pattern is then projected onto the worm by the DMD, allowing for the illumination of the targeted points with a laser. This laser can precisely pinpoint the location of a specific target cell by a simple algorithm specifically designed for the movement analysis of C. elegans.

The impressive spatial and temporal resolution (~50 frames per second) of the ColBeRT technique makes the system scientifically applicable and valid. The ColBeRT’s spatial resolution of  ~30ms allowed Leifer et al. to utilize the technique for a number of manipulatory actions on their transgenic nematodes. When cholinergic motor neurons of transgenic C. elegans were exposed to laser light, forward motor movement was suppressed and either paralysis or backward movement of the worm was propagated. Similarily, single touch receptors of the worms were also genetically modified to be sensitive to light. In a normal worm, a gentle touch will stimulate these receptors, causing the worm to repel in the opposite direction of movement. In transgenic C. elegans, illuminating these specific receptors with the light from a laser was able to affect the direction of the worm’s movement, just as a physical stimulus would have. Even more astounding, HSNs (hermaphrodite specific neurons), which innervate the vulval region of C. elegans, were also able to be genetically modified and stimulated with light exposure. When a thin laser strip was shone on the HSN region of the worms, involuntary egg-laying was evoked.

Although still in its beginning stages, the ColBeRT technique seems to be a promising solution to overcoming one of the primary difficulties standing in the way of neuroscience. ColBeRT not only highlights cell-to-cell interactions, but also identifies the precise actions of specific neurons, something that had never been thought possible in the past. As technology develops further, perhaps we will soon be able to manipulate the cells of more complex organisms and eventually, even mammals. Optogenetics and techniques like ColBeRT may be the key to discovering the subtleties of different neurons and could even potentially help map out the human brain.

Single Worm Neurons Remotely Controlled with Lasers - Scientific American

Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans - Nature Methods

The Samuel Lab videos - Vimeo

Tagged ,

F—— Magnets, How Do They Work?

February 1st, 2011 in News 1 comment

Bookmark and Share

Magnet

It has been said “The most exciting phrase to hear in science, the one that heralds new discoveries, is not 'Eureka!' but 'That's funny...'” (Isaac Asimov), and a recent observation by a Harvard Medical School lab studying the brain chemistry of Bipolar Disorder has researchers uttering that precise phrase...as well as the one alluded to in the title of this post.

The initial study prompting such observations recruited patients suffering specifically from Bipolar Disorder, also known as Manic-Depression, for 20-minute brain scans in an MRI.  MRI scans subject patients to a harmless magnetic field and pulses of radio waves to create detailed structural images of various body parts, in this case, the brain.  While the procedure is painless and relatively short, it can be unpleasant for reasons wholly unrelated to the magnets and radio signals; patients frequently report unrelated bodily discomfort or claustrophobia.  For this reason it was all the more surprising, according to one researcher, that patients participating in the study started to report mood elevations (that for some lasted days or even a week) following the scan.  One patient even subtly suggested that the researchers had slipped her something without her permission.

dn7_transcranial

Patient undergoing TMS treatment for depression

The use of magnets to improve the effects of depression is not uncharted territory in neuroscience and it might even sound familiar to some.  Transcranial magnetic stimulation, or TMS, is another technique that has recently been adapted to depression therapy, yet it is more akin to electroconvulsive, or “electroshock”, therapy (ECT) than MRI.

TMS uses a magnetic field to induce a relatively small electric current, without causing seizure or loss of consciousness, to stimulate the left prefrontal cortex, the area thought to be under-active in depression.  Whereas ECT treatments are utilized only in the most extreme depression cases because of the risk of seizure and necessity of sedation, TMS carries much fewer risks and can be used for more mild depression. While the exact mechanisms are still not known, particularly the roll of seizure for the antidepressant effects, both ECT and TMS have been cleared by the FDA.

But the magnet employed in MRI does not excite specific brain regions (if it did the entire imaging method of functional magnetic resonance imaging, fMRI, would be ineffective) and it is certainly not strong enough to induce seizures.  After observing the curious side-effects of their initial study, the aforementioned researchers set up a small preliminary study with both bipolar and normal controls who confirmed respectively that the effects were not placebo, and that even those without depression can experience the mood-boosting effects of MRI.

So could a new depression treatment soon be joining the ranks of such accidental scientific breakthroughs as penicillin and Post-It notes?  At this point it really is unclear.  The actual mechanism of the mood-boosting effects of MRI on depressed patients is not yet understood, nor have the effects been generalized to unipolar depression.  However, the safety of exposure to MRI has been confirmed by the FDA and a lack of total understanding regarding what causes the “miraculous” effects of that other magnet-based depression treatment, TMS, as well as a host of other medical treatments (including lithium for Bipolar Disorder) certainly has not prevented their use.

Picture Unrelated

Picture Unrelated

Tagged , , , , ,