A medical and neuroscience blog.

Thursday, 3 April 2014

The Four Humours



Claudius Galenus was a Greek philosopher and physician who practiced medicine among the Romans circa AD 160. Galen brought the approach known as Humourism to the mainstream. Humourism is a philosophical theory originating from he Greek philosopher Empedocles who implied that all things are combinations of the four basic elements: earth, water, fire and air. 
Earth: cold and dry
Air: warm and wet
Fire: warm and dry
Water: cold and wet
However, Galen like the father of modern medicine, Hippocrates, believed that these basic elements were mirrored in corpus. Hippocrates stated that the qualities of the four elements are reflected in our bodily fluids namely blood, phlegm, yellow bile and black bile. They both set about classifying illnesses in terms of excess of these fluids (Mukherjee, 2010). 
Excess blood: prompted inflammation: red, warm, painful.
Excess phlegm: prompted "tubercles, pustules, catarrh and nodules of the lymph" (ibid): cold, white, soggy, heavy. 
Excess yellow bile: prompted jaundice: yellow. 

Excess black: prompted depression (or melancholy, literally black (melass) bile (khole) and cancer: oily, viscous, dark. 

Cancer was believed to be the static form of black accumulating into a solid mass (ibid), whereas depression was viewed as the excess of fluid black bile circulating through the system. 
Galen explored this the approach of Humourism further, expanding into a theory of personality. Galen saw a direct relationship between the levels of the humours in the body and the emotional and behavioral inclinations known as temperaments. He described these temperaments as sanguine (blood), phlegmatic (phlegm), choleric (yellow bile) and melancholic (black bile). Imbalances in the humours determined personality as well as susceptibility to certain illnesses. Unfortunately, this interesting yet erroneous belief about illness continued beyond Galen's death in AD 199. Medicine focused all curative and therapeutic efforts in Galen method. Surgery was thought pointless as the humour would only flow back. 

Galen's falsely held beliefs about anatomy stood uncorrected until Andreas Vesalius's attempts to confirm his heroes hypothesis disconfirmed it. Due to Vesalius discontent with the state of anatomical training at the University of Paris, he began to his own exploratory autopsies (ibid). These exploratory autopsies on the bodies left at the city gallows and in poorly covered graces, revealed to Vesalius that the possibility of Galen's theories were non-existent. Blood, yellow bile and phlegm were found aplenty but black bile (the corner stone to Galen's theory) was no where to be found (ibid). Vesalius's discoveries and intricate anatomical drawings soon shattered the idea of humourism, opening up the doors to effective treatment. 

The theory of Humourism, did not however completely disappear. In fact, in psychology a major theory of personality still owes its root to the Greek physicians.
If one of the humours developed uncontrollably, becoming obviously dominant to the other three humours, the corresponding personality type would also become dominant. As a paradigm, a sanguine person has too much blood and as a result shows characteristics such as cheerfulness and optimism but can be selfish and overconfident. A phlegmatic person suffers from too much phlegm and would be rational and consistent but often slow and quiet. A choleric person suffers from too much bile and would be passionate and energetic but could also be tempered. Finally, a melancholic person suffers from excess bile and would be characterised as the artists, poetic and artistic but often depressed and fearful.
During Galen's time, the Medieval Ages and up until the Renaissance it was considered accurate that certain people were born predisposed to one of the four temperaments and imbalances could be cured by changes in diet, exercise or the extremes of purging and blood-letting. By the 1500s, hundreds of errors were found in Galen's work but he would later come to influence Hans Eysenck that concluded that temperaments are in fact biologically based but not through humours. Eysenck identified two personality traits he called neuroticism and extraversion, a nod to Galen.

Citation:
Collin, Catherine. The Psychology Book. New York: DK Pub., 2012. Print.
Mukherjee, Siddhartha. The Emperor of All Maladies: A Biography of Cancer. New York: Scribner., 2010. Print. 

Tuesday, 11 March 2014

Brain Illustrations: Lateral and Cranial View

Lateral View

Cranial View


Wednesday, 29 January 2014

Basal Ganglia Disorders: Parkinson's and Huntington's Disease

My last post was exclusively about basal ganglia and the reason for this was to help clarify the parts of the brain directly involved in two very infamous disorders: Parkinson's and Huntington's Disease.
Image
Parkinson's Disease 
Parkinson's disease is far more recognized that Huntington's disease; however, thanks to the character Thirteen on the tv show House that might be changing. Parkinson's disease effects about 1% of all people over the age of 50; however, as you can see from the video posted below, this is not always the case. Another example is actor Michael J. Fox, who was diagnosed with Parkinson's at the age of 30. He has since become an activist for the cure of Parkinson's, which led him to found the Michael J. Fox Foundation. It is not that uncommon to know someone with the disease. Many people can in fact recognize it based on the very characteristic tremors.

Parkinson's is classified by hypokinesia. The symptoms of Parkinson's include slowness of movement or bradykinesiadifficulty in initiating 'willed' movements or akinesia, increases muscle tone or rigidity, and of course, tremors in the hands and jaws even at rest. Many  of those who suffer from the disease will eventually show signs of cognitive decline. More specifically, the substantia nigra's input to the striatum. This input features the neurotransmitter dopamine, which facilitates the activity of the motor loop by activating cells in the putamen. As noted in the previous post, the putamen forms an inhibitory connection with neurons in the globus pallidus, which then forms an inhibitory connection with the thalamus (VLo). Due to the depletion of dopamine, the 'funnel' between VLo and the supplementary motor area (SMA) closes. As a result, the victim of Parkinson's will have impaired motor function with symptoms such as ones listed above.
Treatment Options for Parkinson's Disease
Even through Parkinson's cannot be cured, therapies do exist to try to ease or deter the symptoms. Most therapies aim at enhancing the levels of dopamine delivered to the caudate nucleus and the putamen. The most common type of medication is known as L-dopa, which is a precursor for dopamine. This means that it participates the chemical reaction that produces dopamine. This treatment does alleviate some of the symptoms; however, it cannot do anything to stop the progressive course of the disease, nor slow the rate of cell degeneration in the substantia nigra. Currently, experiments are being conducted to test whether graftng non-neural cells, manipulated to produce dopamine, into the basal ganglia can help. Also, stem cell research shows promise to one day provide an effective treatment as well.
Huntington's Disease
Whereas Parkinson's is characterized by hypokinesia, Huntington's is characterized by hyperkinesia or excessive movement. As tragic as Parkinson's disease is, Huntington's does seem far more frightening. A hereditary, progressive and always fatal disorder, Huntington's  symptoms include dyskinesia or abnormal movements, dementia and disorder of the personality. The scariest part of the disorder is that the symptoms do not appear until adulthood, so unless the person knows that they have a history of the disorder, they can easily pass on the genes of Huntington's to their children without even knowing that they have it. Genetic tests can be performed to find out for sure, but for many people it is too late at that point. The name Huntington's comes from the abnormal gene carried by the patient. The first and most notable sign of the disease is known chorea: spontaneous, uncontrollable movements with rapid, irregular flow resulting a flicking movement in various parts of the body. In fact, Huntington's disease can also be called Huntington's Chorea. The devastating effects of the disease is due to the profound neuron loss in caudate nucleus, putamen and globus pallidus as well as cell loss in any other part of the cerebral cortex. The fact that Huntington's can strike any part of the brain means that many patients suffer a variety of different symptoms, sometimes making it difficult to diagnose without a genetic test. Damage to the basal ganglia results in a loss of inhibitory output to the thalamus (VLo) resulting in the abnormal movements.
Unfortunately, due to the progressive nature of the disorder and the genetic component, treatment for Huntington's is virtually non-existent. Most patients with the disorder have their symptoms treated with various medications ranging from anti-depressants to sedatives and anti-psychotics.
The man featured in the video above is truly inspiration.
Thank you for reading :)

Sunday, 19 January 2014

Neuroimaging: EEG, MRI, fMRI, MEG, PET and TMS

Too see the old post click here.
Electroencephalogram (EEG)
EEGs measure electrical signals generated by the brain through electrodes placed on the scalp (ibid). Gel or a conduction solution is used to connect the electrodes to the scalp. Electrical signals are produced by partially synchronized waves of neural activity measured in Δ voltage/time (up to 2000 Hz). Signals are able to amplify the waves of neural activity so that sense can be made of them. Waves themselves represent stages of conscious; different frequencies represent different stages. Most of the time our brain is emitting alpha waves, which are of a regular frequency (8-12/sec), high amplitude and represent relaxed wakefulness. Should the wave amplitude decrease, it can indicate neural activity further from the cortex.
When EEG waves accompany physiological events, they are known as event-related potential (ibid). Event-related potentials are calculated by averaging the signal trails epochs, averaging reduces the noise of surrounding activity and increases strength of the signal.
Advantages of the EEG:
-       High temporal resolution (accurate at recording fast changes in neural activity)
-       Less subject to motion artifacts
-       Not claustrophobic
-       Portable
-       Can be used on infants
Disadvantages of the EEG
-       Weak spatial resolution
-       Synchronous firing of 10K neurons is required to produce a magnetic field which is large enough to measure
MRI: Structural and Functional
MRI Machine
MRIs produce high-resolution, three-dimensional images from the measurement of waves that hydrogen atoms emit when they are activated by radio frequencies waves in a magnetic field (Pinel, 2011). High spatial resolution means MRIs are able to detect and represent different spatial locations. The images produced are far clearer than CT scans; however, fMRIs are seen as even greater improvement.
The fMRI produces images that represent increased oxygen flow in response energy needs of specific brain regions. Oxygenated blood has magnetic properties due to its high iron content making it sensitive to magnetic fields emitted from protons in the MRI. Deoxygenated blood is not sensitive to magnetic fields; as such brightly light portions of the fMRI reflect high-energy consumption. If you want to read, more about the BOLD fMRI click here, BOLD stands for blood oxygen level dependent signal. The job of the fMRI is to record this BOLD signal.
Advantages of the fMRI
-       Accurately depecits structural data
-       Reasonable temporal resolution
Disadvantages of the fMRI
-       Claustrophobic
-       Noisy (literally, not signal noise)
-       Very susceptible to movement artifacts
-       No metal-based equipment can be around the machine
-       BOLD is not a direct measure of neural activity, only oxygen consumption
Magnetoencephalogram (MEG)
MEG
The MEG measures changes in magnetic fields on the surface of the scalp (ibid). Unlike the fMRI, magnetic fields are produced by changes in neural activity, which activate pyramidal cells of the cortex. Neural activity is not being affected by magnetic fields.
Advantages of the MEG
-       High temporal resolution
-       Acceptable spatial resolution
-       Compared to an EEG, it is less distorted by the scalp
Disadvantages of the MEG
-       Just like the EEG, it requires a high baselines firing rate in order for a magnetic field to be produced
-       Normally it has to be paired with an MRI
-       Expensive
-       Not portable
Positron Emission Tomography (PET)
PET scan
The PET scan is a bit more controversial than some of the other scans because it involves injecting a radioactive substance. Specifically, 2-deoxyglucose is injected in the carotid artery. This substance is used because of its similarity to glucose, a quality which neurons like very much. Neurons take 2-DG into their system, but cannot metobolise it. The result accumulates in active regions of the brain resulting in measurable levels of radioactivity.
Advantages of the PET:
-       Reasonable structural accuracy
-       Direct reflection of current activity
-       No motion artifacts
-       Not claustrophobic
Disadvantages of the PET:
-       Radioactive substance is involves
-       No temporal resolution and no structural information
-       Poor spatial resolution
-       Expensive and not very portable
Transcranial Magnetic Stimulation (TMS) 
TMS
In 1985, Tony Barker invented the TMS, which is now known for its ability to prove a particular brain activity causes certain behaviour. A non-invasive technique, the TMS causes depolarisation and hyperpolarisation of neurons in the brain. Electromagnetic induction causes a weak electrical current in the cortex to evoke synaptic potentials. With the TMS it is possible to create a stimulated temporary lesion of the brain by preventing normal brain function without causing any adverse effects.
Advantages of the TMS
-       Almost portable
-       Can  prove causality
-       Can simulate a lesion
Disadvantages of the TMS
-       Difficult to specify precise regions of the brain
-       Only surface regions are detectable

Monday, 18 November 2013

Heroin and the Brain

According to the medical journal the Lancet (2007), heroin is the most deadly and addictive of the twenty most common recreational drugs. Even though heroin does not carry the allure of cocaine, heroin usage is still an international problem. An opiate drug extracted from the opium poppy, heroin is an extremely potent analgesic (NHS). Remarkably, the effects of heroin can remain for up to five hours, and a single use is enough to fuel a life-long addiction.
Introduction
Heroin and the other opiates (morphine, codeine, etc.)  when taken orally or inhaled must undergo first-pass metabolism, which decreases the potency of the drug (Sawynok, 1986). However, when heroin is injected it is able to by pass the blood-brain barrier as well as the fast-pass system. Once inside the brain, heroin breaks down into three different components, the quintessential and final form being morphine (Dubuc, 2002).  Morphine, an μ-opioid agonist, binds to μ-opioid receptors present in the brain, spinal cord and gut. The binding of the morphine to these receptors creates the sedative, euphoric and pain-relieving effects. The pleasurable feelings produced the heroin are positively reinforcing because they activate the limbic system or pleasure centre of the brain.
The High
Prior to heroin entering the system, inhibitory neurotransmitters (GABA) are active in the synapse (Dubuc, 2002). These inhibitory neurotransmitters inhibit dopamine  from being released. Natural opiates (endorphins, enkephalins, etc.) block the release of neurotransmitters that inhibit dopamine release. As such, when the natural opiates attach to the opioid receptor dopamine floods into the synapses. Heroin mimics the natural opiates released by our system when morphine attaches to the opiate receptor. The release of dopamine causes an immediate sense of welling being or euphoria, sedation and pain-relief.
Physiological Symptoms 
Just like with cocaine abuse the effects are not just limited to the brain. Addiction not only destroys relationships and financial security; overdose does not need to be the only cause of death.
Pharmacology 
Heroin was first synthesised by C.R. Adler Wright in 1874 when he added two acetyl groups to the morphine molecule (Sawynok, 1986).  Morphine itself comes from latex harvested from green capsules of the opium poppy. The use of opium predates written history with evidence of the poppy found in Mesopotamia. Wright's discovery of heroin, however, was largely ignored until it was accidentally re-synthesised by Felix Hoffman of what is now Bayer pharmaceutical company. Hoffman ironically was trying to synthesise codeine (a less addictive and less potent form of morphine), however, instead also produce an acetylated form of morphine otherwise known as heroin (Chemical Heritage Foundation, 2010).
The medical name for heroin is diacetylmorphine or morphine diacetate otherwise known as diamorphine. Today heroin is known by a variety of street names including H, horse, black tar, brown and smack.
Heroin Addiction 
As with all other drugs that work on the reward-system, overtime pleasure experienced by the excess release of dopamine diminishes. As a result, an addict must increase their dosage to experience the same high. It is often by addicts that no high ever measures up to the first one. Remarkably, this shows how quickly the drug effects our normal ability to feel pleasure and relief.
Physiological and psychological effects of addiction (Timberline Knolls Residential Treatment Center, 2013):
- Dry mouth
- Cycles of hyper alertness followed by extreme drowsiness
- Disorientation
- Sudden behavioural changes
- Constricted pupils
- Shortness of breath
- A droopy appearance
Heroin Overdose and Treatment 
Like all class A drugs, the risk of heroin overdose is common. As such it is important that these symptoms are recognised by medical professionals as well as anyone else witnessing any of the following (U.S. National Library of Medicine, 2013):
- Spasms  of the stomach and/or intestinal tract
- Low blood pressure
- Weak pulse
- Dry mouth
- Extreme pupil constriction
- Tongue discolouration
- Slow, shallow or no breathing
- Bluish nails and lips
- Delirium
- Disorientation
- Constipation
- Extreme drowsiness
- Muscle spasticity
- Coma
Even if you are not medical professional, if you notice any of these symptoms you should call poison control.

Citations:
Dubuc, Bruno. "THE BRAIN FROM TOP TO BOTTOM." THE BRAIN FROM TOP TO BOTTOM. Douglas Hospital Research Centre, Sept. 2002. Web. 17 Nov. 2013.
"Felix Hoffmann." Homepage of the Chemical Heritage Foundation. N.p., 2010. Web. 17 Nov. 2013.
"Heroin Addiction Symptoms and Effects." Heroin Addiction. Timberline Knolls Residential Treatment Center, 2013. Web. 17 Nov. 2013.
"Heroin Overdose: MedlinePlus Medical Encyclopedia." U.S National Library of Medicine. U.S. National Library of Medicine, 31 Oct. 2013. Web. 17 Nov. 2013.
Nutt, David, et al. "Development of a rational scale to assess the harm of drugs of potential misuse." The Lancet 369.9566 (2007): 1047-1053.
Sawynok, Jana. "The therapeutic use of heroin: a review of the pharmacological literature." Canadian journal of physiology and pharmacology64.1 (1986): 1-6.

Thursday, 31 October 2013

Basal Ganglia: Substance P

As mentioned in my last post on basal ganglia, the majority of the striatum consists of medium spiny neurons. These medium spiny neurons are GABAergic and organised based on the peptide they contain as well the dopamine receptors they contain. One these peptides is called substance P (SP). As a neuropeptide, SP functions as a neurotransmitter as well as a neuromodulator. Other than GABA, SP functions as a neurotransmitter in MSNs. Specifically, SP-releasing neurons mediate "synaptic communication between MSNs" (Blomeley, et al. , 2009). 
MSN
Previously it was thought that striatal projection neurons like MSNs only inhibit each other; however, a study by Blomeley, et al. , 2009 has proven that they can also interact in an excitatory manner. Studies have shown the synaptic NK1 receptors, whose major receptor molecule is SP are present in a glutamteric terminals in the stiratum (Jakab et al., 1996). In the study by Blomeley, the importance of these NK1 receptors was investigated. The results suggest that SP plays a crucial role in facilitating the release of glutamate between medium spiny neurons. In other words, communication between the neurons is increased by SP attaching NK1 receptors found on the terminals of glutamate releasing MSNs. 
Citations:
Blomeley, C. P., Kehoe, L. A., & Bracci, E. (2009). Substance P mediates excitatory interactions between striatal projection neurons. The Journal of Neuroscience29(15), 4953-4963.

Sunday, 13 October 2013

The Striatum

The striatum is the largest collection of neurons in the basal ganglia. Composed of the caudate nucleus and putamen, the basal ganglia, as the name suggests, sits at the base of the cerebrum. It receives input from regions of the cerebral cortex, the limbic system, and the sensorimotor and motivational systems via the thalamus. In addition to the cerebrum, the striatum receives input from the brainstem including the substantia nigra and the raphe nuclei of the reticular formation. The dopamine and serotonin of these two structures serve a modulatory function. Anatomists organise the striatum on the "basis of differential connectivity and distribution of neurochemical markers" (Redgrave, 2007). Processing strong excitatory input, the striatal neural circuits generate a strong inhibitory output, which controls the output of basal ganglia further along in the motor loop.
300px-Basal_Ganglia_fig3
The major cytology of the striatum is GABAergic medium spiny neurons (MSN), making up about 95% of the total cellular structure. MSNs are organised into two groups based on the peptide they contain, substance P and enkephalin and the proportion of dopamine receptors (D1 or D2) they contain. MSNs create dense networks of axon collaterals. As projection neurons, the MSNs create this dense network by forming axon collaterals with one another. Tunstall et al, 2002 found that almost 30% form an axon collateral with a neighbouring MSN. Research has shown that the function of these collaterals is in cellular recognition and "classification of cortical patterns" (Blomeley, et al. , 2009).
The striatum is a vital part of the basal ganglia, and all pathways run through it. From the striatum onwards, the pathway either becomes direct or indirect. As shown in the figure below.
Screen Shot 2013-10-13 at 17.35.29
Citations:
Blomeley, C. P., Kehoe, L. A., & Bracci, E. (2009). Substance P mediates excitatory interactions between striatal projection neurons. The Journal of Neuroscience29(15), 4953-4963.
Redgrave, P. (2007). Basal ganglia. Scholarpedia, 2(6): 1825.