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.
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.
Blomeley, C. P., Kehoe, L. A., & Bracci, E. (2009). Substance P mediates excitatory interactions between striatal projection neurons. The Journal of Neuroscience, 29(15), 4953-4963.
Redgrave, P. (2007). Basal ganglia. Scholarpedia, 2(6): 1825.
he nervous system is the body’s speedy, electrochemical communication system. It consists of all the nerve cells of the peripheral and central nervous systems.
The central nervous system consists of the brain and spinal cord. The peripheral nervous system is the sensory and motor neurons that connect the central nervous system to the rest of the body. Nerves are the neural cables of the nervous system containing many axons. They are part of the peripheral nervous system. They are connected to the central nervous system by muscles, glands, and sense organs.
Sensory neurons carry incoming information from the sense receptors to the central nervous system. Interneurons are part of the central nervous system. They internally communicate and intervene between the sensory inputs and motor inputs. They are the most common type of neuron. Motor neurons carry outgoing information from the central nervous system to the muscles and glands.
– The Peripheral Nervous System –
The peripheral nervous system is made up of the somatic nervous system and the autonomic nervous system. The somatic nervous system controls the body’s skeletal muscles. The autonomic nervous controls the glands and muscles of the internal organs. It is broken down into the sympathetic and the parasympathetic nervous system. The sympathetic nervous system arouse the body, mobilising its energy in stressful situations (fight or flight response). The parasympathetic nervous system calms the body, conserving its energy.
– The Central Nervous System –
The spinal cord is the information highway connecting the peripheral nervous system to the brain. Ascending neural tracts send up sensory information. Descending neural tracts send down motor control information. Reflexes are the body’s autonomic response to stimuli controlled by the spinal cord. They are composed of 1 sensory neuron and 1 motor neuron that communicate through one interneuron. Because they only run through your spinal cord, they react automatically without your brain being involved in the process. The spine sends information back to the brain. Bodily pain or pleasure is controlled by the brain.
The brain receives information, interprets it and then decides on a response. It functions like a computer, receiving slightly differing images of an object from the eyes, it computes the differences and infers how far the object must be to project such a difference.
Neural networks are interconnected neural cells which, with experience, can learn, as feedback strengthens or inhibits connections that produce certain results. Stephen Kosslyn and Oliver Koening proposed to think of neural networks as networks of people. Neuron network with nearby neurons with which the can have short, fast connections. Each layer of a neural connects with various cells in the next layer. Learning occurs as feedback strengthens connections that produce certain results. New computer models simulate this process plus the excitatory and inhibitory conniptions to mimic the brain’s capacity for learning.
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.
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.
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.
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.
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.
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
– 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
– Extreme drowsiness
– Muscle spasticity
Even if you are not medical professional, if you notice any of these symptoms you should call poison control.
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.
The cerebral cortex is the intricate fabric of interconnected neural cells that covers the cerebral hemisphere. It serves as the ultimate control and information processing centre. Humans have larger cortexes which enables us to be more adaptable, which gives us the ability to learn and think beyond basic survival instincts.
The cerebral cortex is made up of a sheet of cells that is 1/8 of an inch think and contains approximately 30 billion nerve cells. Glial cells or glue cells as they are commonly called, hold the nervous system together. They are NOT neurons but their own category of cells. Glial cells serve to support, nourish and protect neurons by communicating with them. Scientists are currently attempting to find connection between glial cells and information transmission and memory.
Folds of the brain increase the brain’s surface area allowing for maximised function and activity. As most people know, the brain’s cerebral cortex consists of four lobes: the parietal lobe, the occipital lobe, the temporal lobe and the frontal lobe. The frontal lobe is the front portion of the cerebral cortex, lying right behind the forehead. The frontal lobe is involved in speaking, muscle movement, high level cognition (planning, judgment, reasoning). Damage to the frontal lobe can result in changes in social skills, libido, attention and risk-taking. The parietal lobe is the part of the cerebral cortex at the top of head, behind the frontal lobe towards the back. It includes the sensory cortex. This means the parietal lobe processes sensory information such as pain, touch and pressure. Damage to the parietal lobe results in sensory problems such as impaired verbal memory and language skills. The occipital lobe lies at the base of te head and includes the visual areas; it receives visual information from the opposite visual field. This means that what is seen by our right is processed by the left side of our occipital lobe and vice versa. The temporal lobe lies above the ears and includes the auditory areas. These two areas receive auditory information from the opposite ear much like how the eye and occipital lobe work.
– Functions of the Cerebral Cortex –
German physicians Fritsch and Hitzig electrically stimulated the cerebral cortexes of dogs. Through their experiments, Fritsch and Hitzig found that they could make different parts of the dogs’ bodies move. However, their ability to make the dogs move through stimulation was selective. Movement was only observable when a specific arch-shaped area of the back of the frontal lobe was stimulated. This area is know known as the motor cortex. Furthermore, the physicians discovered that the parts of the body that were moved, corresponded to stimulation on the opposite side of the brain.
Neurosurgeons Foerster and Denfield also investigated the functions of the cerebral cortex through stimulation. They found that precise control requires the greatest amount of cortical space. Furthering this idea, Jose Delgado found that specific parts of the cerebral cortex correspond with certain actions. Today it is evident, through the use of MRI scans, that precise actions require overlapping cortical sites.
The cerebral cortex specialises in receiving information from the skin senses and the movement of body parts. The greater the area devoted to specific body region, the more sensitive this area becomes. As a paradigm, our lips are far smaller than our back; however, relative to size, the cerebral cortex dedicates far greater area to our lips making them far more sensitive and kisses so enjoyable. It also explains why our backs are far less sensitive to pain than say our stomachs.
– Association Functions –
The association areas consist of 3/4 of the cerebral cortex. Association areas are uncommitted to sensory of muscular activity. They associate with various sensory inputs with stored memories. The functions of the association areas cannot be triggered by stimulation or any other forms of probing. The existence of these areas are vital in disproving the popular belief that 90% of our brain is dormant. Our brain relies heavily on these unassociated areas for interpretation, integration and acting on processed sensory information.
Cherry, Kendra. “The Anatomy of the Brain.” The Four Lobes (2012): n. pag.Psychology. Web. 03 Sept. 2012. <http://psychology.about.com/od/biopsychology/ss/brainstructure_2.htm>.
Myers, David G. Psychology . 6. Worth Publishers, 2001., David G. Psychology . 6. Worth Publishers,2001. Print.
Raichle et al.
When Raichle et al. conducted their PET study in 80s and discovered increased blood flow to the V1 he also measured oxygen consumption and glucose consumption. He found that blood flow increased by around 50%, glucose consumption increased by around 50% but there was hardly any change in oxygen consumption (Jones, 2013). This is inconsistent with modern findings. Take the dip shown in fMRI studies, there is clearly a change in oxygenation levels. The increase in doexyhemoglobin is seen as a evidence for oxygen consumption and the overshoot of oxyhemoglobin is seen as evidence of increased blood flow. As mentioned in part 2, this dip is associated with a greater spacial resolution than during any other part of the hemodynamic response (ibid). However, in some studies this dip is not present.
However, recent PET scans have been able to show an increase in oxygen consumption. The best explanation for this missing data is flaws in the PET scan itself. PET scans have poor spatial and poor temporal resolution, which means if oxygen were to be picked up due to spatial or temporal differences (differences in location and processing speed) it would be very difficult to pick it up.
Hypercania, fortunately, is a more reliable way of measuring for oxygen consumption. Hypercapnia is the term used for elevated levels of carbon dioxide in the blood stream. As carbon dioxide is a waste product of aerobic metabolism (oxidative or cellular respiration), if we change the amount we breathe in or use oxygen there will be an increase carbon dioxide levels. All parts of the body that can detect carbon dioxide other than the brain maintain neural activity when we become hypercanic. As a result, hypercania acts as a ‘control’ condition for comparing blood oxygenation increase following increased cerebral blood flow to blood oxygenation increase due to neural activity.
Cerebral blood flow increase due to hypercania will result in an oxygenation increase.
Cerebral blood flow increase due to increased neural activity will have a lower oxygenation increase. This is because oxygen has been consumed for the increased neural activity to be possible.
The Diffusion Limited Theory
Buxton & Frank (1997) decided to tackle why if oxygen consumption increases by so much, why does cerebral blood flow need to increase even more. Buxton & Frank (1997) believed the answer to that question was a gradient. In order to get more oxygen to the brain, you either need more oxygen in the blood than in the brain or less oxygen in the brain than in the blood. This creates a gradient that will allow oxygen to diffuse from the blood to the brain. As the level of available oxygen (oxygen tension) in the brain at rest is almost or around zero, the only way to create a viable gradient is to increase the amount of oxygen in the blood vessels namely through blood flow.
Buxton and Frank believed the disproportional amount of oxygen consumption compared the blood flow is due the high speed of the blood flow. The blood passes through the brain too quickly for all the oxygen to be consumed. As a result, we have a high speed flow to continuously supply oxygen where necessary, but this unfortunately is not very efficient as the process of consuming the oxygen compared to the flow is disproportionate.
JONES, M. (2013). Referencing and citation – Harvard style, from PSY108 Neuroscience and Evolution. University of Sheffield, Richard Roberts Building on 8th March. Available from: Blackboard.
Action potential is something I find a lot of people who study psychology or neuroscience struggle with. For me, I just could never remember where it was sodium or potassium on the inside or outside of the cell membrane. Luckily, action potential is not as difficult to understand when you break it down into its major subsections.
Action potentials are generated by neurons and are always consistent in size and duration; their strength does not diminish as it propagates down the axon. The strength of the action potential is determined by the frequency it propagates down the axon; the frequency and pattern of the action potentials generate a code used by neurons to transfer information appropriately from one location to another. Neuroscientists use an oscilloscope to study action potential as it sensitive to changes in voltage over time. The action potential works its way down the axon until it reaches the axon terminal. At the axon terminal, a synaptic transmission is initiated.
Generating the Action Potential and All-or-None
The perception of any sensation such as warmth or pain as well as any movement is the direct result of action potential. Depolarization of the neuron is what is necessary for an action potential to be generated, and it can arise in a variety of ways depending on the kind of neuron. The most common way to depolarize a neuron is by entry of sodium ions. The important thing is that the stimulus is strong enough to depolarize the neuronal membrane. Action potential works on what is known as all-or-none response, meaning it works on a threshold basis. As it is consistent in size, it relies on the stimulus exceeding a threshold called generator potential in order to fire, rather than the strength of the stimulus itself. This may seem confusing because yes, the strength of the stimulus must exceed the threshold , so in a way strength of the stimulus matters. However, what is important to remember is that once the threshold has been exceeded, the strength of the stimulus has no importance or effect on the strength of the action potential whatsoever.
Properties of Action Potential
The membrane of a neuron at rest is around -65mV or -65 milli-volts with the regard to the outside. Volts is a good indicator that we are dealing with electrical current. During action potential, however, the membrane potential becomes briefly positive. This change from a negative to positive membrane potential is depolarization. Depolarization, a very rapid process, will continue until the membrane potential reaches 40 mV. To give you an idea how rapid the entire process of action potential including reaching back to -65mV it takes 2 milliseconds.
An action potential will only ever travel in one direction because of the refractory period. When the action potential travels away from the soma or cell body towards the axon terminals it is called orthodromic conduction. When the action potential travels towards the soma, the action potential is called antidromic conduction. Regardless of the direction it is traveling, action potential conductance rate varies, but the typical rate is 10m/s. The average length of an axon is about 2cm.
1. Resting Potential: As stated before, the resting membrane potential is around -65 mV but it ranges depending on the neuron. Different textbooks will tell you different resting membrane potentials, but it’s not something you need to worry too much about. It is also important to note than Vm or the membrane action potential is equal to 0. Vm=0.
Threshold: The membrane potential at which there stimulus is strong enough to open the sodium channels. The opening of the voltage-gated sodium channels changes the ionic permeability of the membrane in favour of sodium.
3. Rising Phase: As the membrane potential is negative at the resting phase, the opening of the sodium channels creates a great pull. This is because the sodium ions (Na+) are positive. The result is sodium ions rushing into the cell causing rapid depolarisation. This changes the membrane action potential towards the equilibrium value of sodium or ENa.
4. Falling Phase: The voltage-gated sodium channels become inactivated, and in turn the voltage-gated potassium channels open. This time around, there is a great pull on the potassium ions (K+, also positive) outside the cell as the sodium ions have made the membrane potential very positive. Potassium ions rush outside the cell, resulting in a negative membrane potential once more, close to Ek or the equilibrium value of potassium.
Undershoot: The membrane potential is more negative than -65 mV.
Absolute Refractory Period: The cell cannot fire during this period as there is a gradual restoration of the membrane potential back to -65mV and the Vm to 0. During this time, even if the stimulus is strong enough to exceed the threshold, the membrane will not fire. It lasts about 1ms.
Relative Refractory Period: The membrane potential stays hyper-polarised or at the undershoot until the potassium channels close. It can be difficult to initiate another action potential even after the absolute refractory period, longer than 1 ms.
Factors Influencing the Conduction Velocity
The rate of the action potential depends on the strength of the depolarising current; specifically, it is reflected in firing frequency of the action potential. The maximum frequency, however, is 1000 Hz. Generally, axon potential conduction velocity increases diameter of the axon as well as the size of the axon itself and the number of ion channels. Smaller axons tend to require a much greater stimulus to reach the threshold necessary for depolarisation, as such as they are more sensitive to local anaesthetics.
The majority of the cranial nerves emerge from the brain stem on the ventral surface of the brain. Cranial nerves I and II emerge from the forebrain and cranial nerve XI from the brain stem as well as the spinal cord. As they are nerves they are classified as part of the peripheral nervous system; however, two of the cranial nerves are also considered part of the central nervous system, I and II. Each nerve often has fibers performing many different functions. Also they have associated cranial nerve nuclei in the midbrain, pons and medulla of the brainstem.
I. Olfactory: a special sensory cranial nerve responsible for our sensation of smell.
II. Optic: a special sensory cranial nerve responsible for our sensation of vision.
III. Oculomotor: a somatic and visceral motor cranial nerve responsible for the movement of the eye and eyelid as well as the parasympathetic control of pupil size.
IV. Trochlear: a somatic motor cranial nerve responsible for the movements of the eye.
V. Trigeminal: a somatic sensory and motor cranial nerve responsible for the sensation of touch on the face and the muscles of mastication.
VI. Abducens: a somatic motor cranial neuron responsible for the movements of eye.
VII. Facial: a somatic and special sensory cranial neuron responsible for the movement of muscles of facial expressions as well as the sensation of taste in the anterior 2/3 of the tongue.
VIII. Auditory-vestibular: a special sensory motor neuron responsible for the sensation of hearing and balance.
IX. Glossopharyngeal: a somatic and visceral motor cranial neuron as well as a visceral and special sensory cranial neuron responsible for the movement of muscles in the throat and the parasympathetic control of salivary glands in addition to the detection of blood pressure changes in aorta and the sensation of taste in posterior one third of tongue.
X. Vagus: a visceral motor and sensory cranial neuron as well as a somatic motor neuron responsible for the parasympathetic control of heart, lungs and abdominal organs as well as the sensation of pain associated with the viscera and movement of muscles in the throat.
XI. Spinal accessory: somatic motor neuron responsible for the movement of muscles in the throat and neck.
XII. Hypoglossal: a somatic motor cranial neuron responsible for the movement of the tongue.
Bear, Mark F., Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. Philadelphia, PA: Lippincott Williams & Wilkins, 2007. Print.
My most recent post showcased the artist Isti Kaldor who has bipolar disorder. This post will explain the basics of the disorder. Quite a few celebrities have come forward stating they have bipolar disorder including Catherine Zeta Jones, Demi Lovato and Stephen Fry. If you want to know the true scope, there is a wikipedia page dedicated to celebrities known to have it. Despite their very public work lives, with our limited insight into their personal lives it is difficult to really know much about the disorder. Stephen Fry, however, did a brilliant documentary on his experiences dealing with his bipolar disorder called Stephen Fry: The Secret Life of the Manic Depressive, which is available in full on YouTube.
Symptoms and Types
As the title says, bipolar disorder is sometimes also called manic depression, but bipolar disorder is its official name. Characterised as a recurrent mood disorder, it consists of repeated episodes of mania interchanged with episodes of depression. The depressive episodes include similar but less severe symptoms of major depression such as changes in appetite, insomnia or hypersomnia, fatigue, feelings of worthlessness, guilt, inability to concentrate and suicidal thoughts. As such, the symptoms can be managed with anti-depressants. The manic periods, however, are the opposite in some respects. Symptoms consist of grandiosity, decreased need for sleep, talkativeness, flight of ideas, short attention span, and impaired judgement. It is believed that the correlation between bipolar disorder and celebrities is that those with the disorder usually experience these manic highs with bursts of creativity and inspiration. Unfortunately, the manic period can also result in promiscuity and complete loss of inhibition much like the effects of alcohol. As with any disorder, the range and complexity of symptoms varies greatly from person to person.
Bipolar comes in two general forms: type I and type II. Type I is marked by manic episodes (with or without incidents of major depression), and occurs in about 1% of the population, equally among men and women. Type II is marked by hypomania (milder form of mania that is not associated with marked impairments in judgment of performance) and is always followed by milder depressive periods.
Numerous twin studies and most notably the one conducted by McGuffin and colleagues (2003) have shown that there is a high concordance between monozygotic twins with “67% MZ vs. 19% DZ.” Also, even though there is a high correlation with depression and mania, the manic component appears to be significantly more heritable in monozygotic twins. We do know that bipolar disorder affects our neurochemical pathways as treatment of lithium and anti-depressants do help alleviate the drastic mood swings. However, the actual structural component is yet to be properly determined. Studies by Bearden et al., 2001 admit that even though “dysfunction is implicated in bipolar illness patients supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions” there is still not enough conclusive evidence to draw a clear link between right hemisphere dysfunction and bipolar disorder.
Strakowski et al., 2005 on the other hand using MRIs have found compelling examples of damage to the prefrontal cortical areas, striatum and amygdala that predates that onset of symptoms, which suggests that abnormal brain structure could in fact play a quintessential role in onset of the disease. Furthermore, if further studies can confirm these findings, it could offer psychiatrists and neurologists a revolutionary way of pre-symptomatic diagnosis. As of 2012, Strakowski et al. have reached a “general consensus” that bipolar type I occurs due to abnormalities within networks that control emotional behaviour such as the prefrontal cortex and limbic area, specifically the amygdala.
To date the most effective treatments for bipolar disorder include lithium (used to target the manic episodes), anti-depressants such as SSRIs, monoamine oxidase and tricyclics. Other types of medication such as anti-anxieties and anti-psychotics are used in some cases depending on the severity of the symptoms. In addition to medication, therapy has also been proved to significantly reduce the psychological stress of the disorder.
Bear, Mark F., Barry W. Connors, and Michael Paradiso. Neuroscience: Exploring the Brain. Baltimore, MD: Lippincott Williams & Wilkins, 2006. Print.
Bearden, C. E., Hoffman, K. M. and Cannon, T. D. (2001), The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disorders, 3: 106–150. doi: 10.1034/j.1399-5618.2001.030302.x
Malliaris, Yanni,. “1.7 Aetiology of Bipolar Disorder.” 1.7 Aetiology of Bipolar Disorder., 20 Aug. 2010. Web. 03 Aug. 2013.
Strakowski, S. M., Adler, C. M., Almeida, J., Altshuler, L. L., Blumberg, H. P., Chang, K. D., DelBello, M. P., Frangou, S., McIntosh, A., Phillips, M. L., Sussman, J. E. and Townsend, J. D. (2012), The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disorders, 14: 313–325. doi: 10.1111/j.1399-5618.2012.01022.x