Huntington’s disease is a neurodegenerative genetic disorder that greatly affects muscle coordination and cognition. The nerve cells in the brain slowly breakdown and atrophy. Huntington’s disease affects the striatum of the brain as well as the hippocampus, purkinje cells, and the cerebellum.
Huntington’s is an autosomal dominant genetic disease that results from a defect on chromosome #4. The defect causes a repeat in a CAG sequence on the DNA to occur many more times than normal. In person without Huntington’s, the CAG sequence is repeated 10 to 35 times. In an individual with Huntington’s disease, the repeat can be repeated 36-120 times. The repeated sequence is expanded as it is passed through one generation to the next, lengthening the sequence in each offspring. Therefore, the disease becomes progressively juvenile. If one parent has Huntington’s, the child has a 50% chance of having the disease as well.
There are two types of Huntington’s: juvenile which appears in children and the much more common form, adult-onset Huntington’s which appears in an individual aged 30 to 40.
Huntington’s disease has become a target due to the ethical issues associated with it. Many question when an individual should be tested for the disease, if at all. Preimplantation genetic diagnosis has been used as a selective form of abortion. Some individuals who might have the disease may opt to not have the disease diagnosed.
Worldwide, 5-10 people out of 100,000 have the disease.
After the first onset of symptoms, an individual typically has a life span of twenty more years of life. Huntington’s has no cure and ultimately leads to death. Suicide is one of the greatest cause of fatalies in the disease with 7.3% with Huntington’s taking their own lives and up to 27% attempting suicide.
Diagnosis: A genetic counselor can determine if the child will have Huntington’s disease using genetic testing. The geneticist will look at the number of CAG repeats and determine the likelihood of the person developing Huntington’s in their life. In most cases, the affected individual will have an idea of when the symptoms will onset. A physical diagnosis that analyzes the symptoms of Huntington’s is also effective for most patients. Medical imaging of the brain can also show which areas of the brain have atrophied.
Symptoms: Huntington’s disease affects many parts of the body. Movement disorders can include involuntary jerking, sustained contraction of muscles, rigidity, diffulty with speech, posture problems, and difficulty swallowing. Cognitive disorders include difficulty with organization, emotional flexibility, lack of focus and reasonable thinking, and various other symptoms. Lastly, psychiatric disorders include sadness, unhappiness, social withdrawal, loss of interest, fatigue, feelings of guilt, reduced appetite, and reduced sex drive.
Treatment: There is no cure for Huntington’s disease. Some of the symptoms can be controlled with various antidepressants and other drugs that reduce the amount of involuntary muscle jerking.
Additional Information: Huntington’s disease has become prominent in different media sources and has appeared in Everwood, House, Private Practice, ER, and Scrubs.
- 24th June
2011 - 24
- 3rd May
2011 - 03
Anatomically Distinct Dopamine Release During Anticipation and Experience of Peak Emotion to Music
Music has long been recognized as both an abstract and rewarding stimulus that produces feelings of euphoria and pleasure in many listeners. Music may also elicit emotional responses from listeners and alter affective states. While music has been present across multiple cultures and societies throughout time, the experience of pleasure while listening to music is highly specific, personal and subjective. In a study featured in Nature Neuroscience last February, Salimpoor and others set out to study what goes on in the brain of individuals while they listened to enjoyable/pleasurable music.
For the study, subjects were asked to bring their own pleasurable music, and the other subjects’ music was used as neutral music for comparison. Dopamine release while listening to music was estimated indirectly by using ligand-based positron emission tomography (PET) scan in which 11C raclopride, a radioactively labeled ligand, competes with endogenous dopamine for D2 receptor binding. The assumption is that if brain areas are experiencing surges of dopamine release, they binding capacity of 11C raclopride will decrease in these areas. The experience of feeling chills, a marker of peak emotional responses to music, was self-reported by the subjects. In addition, psychophysiological measurements (i.e. respiration rate, heart rate, skin conductance, temperature) were also conducted while the subjects listened to music while undergoing PET scanning.
PET scanning revealed changes in 11C raclopride binding in the striatum, specifically in the right caudate and the right nucleus accumbens. There was also a significant positive correlation between reports of chills and feelings of overall pleasure, perhaps indicating that chills may serve as an objective measure of pleasure while listening to music. The experience of overall greater pleasure while music listening was also correlated with greater autonomic nervous system arousal, as indexed by changes in psychophysiological measurements.
To assess the temporal dynamics in dopamine release, the group employed functional magnetic resonance imaging (fMRI) while subjects listened to neutral or pleasurable music. Subjects were asked to press a button whenever they felt chills (typically during pleasurable moments), and the 15s prior to the pressing of the button, which indicated chills + pleasure, were denoted as the anticipation window. Thus, dopamine release was studied in two different time periods: anticipation period (15s before reported pleasure and chills), and peak response (chills/pleasure).
When the fMRI scans were conjoined with the PET masks, the group was able to identify a temporally mediated BOLD response in the right side of dorsal (caudate) and ventral (nucleus accumbens) striatum that corresponded with anticipation epochs and peak experience, respectively. Moreover, as demonstrated above, behavioral measures like the number of reported chills were more correlated with 11C raclopride binding changes in the right caudate while intensity of chills and overall degree of reported pleasure were more significantly correlated with changes in 11C raclopride binding potential in the right nucleus accumbens.
In summary, the experience of pleasure while listening to music acts on the brain similarly to other rewards like food, sex and drugs. Listening to pleasurable music targets striatal areas associated with mesolimbic reward circuitry and dopaminergic neurotransmission.
Source:
Salimpoor, et al. 2011. Anatomically Distinct Dopamine Release During Anticipation and Experience of Peak Emotion to Music. Nature Neuroscience. doi:10.1038/nn.2726
- 31st January
2011 - 31
Brain scans of addiction.
So interesting!
The areas that light up (including the nucleus accumbens) comprise the ventral striatum, an important structure whose dopaminergic innervation is thought to contribute to motivational/emotional salience processes.
- 9th June
2010 - 09
I took these pictures last semester.
We were being taught how to do immunocytochemistry, a laboratory technique in which a specific antibody is used to detect the presence of a particular antigen or protein in a cell. Because the antibody is specific for the protein of interest, it binds the protein and allows visualization by staining and examination under a microscope. Naturally, darker staining relates to protein concentration in those particular areas.
We were given an antibody and were told to determine what protein it was specific for by staining and visualizing our samples. After a long search, I came up with Calbindin D, a calcium-binding vitamin D dependent protein which helps transport calcium. It’s localization includes the cerebellum & cerebellar cortex, the hippocampus and the dentate gyrus, as well as the striatum and other components of the basal ganglia.
