Perineuronal net

Perineuronal nets (PNNs) are specialized extracellular matrix structures responsible for synaptic stabilization in the adult brain. PNNs are found around certain neuron cell bodies and proximal neurites in the central nervous system. PNNs play a critical role in the closure of the childhood critical period, and their digestion can cause restored critical period-like synaptic plasticity in the adult brain. They are largely negatively charged and composed of chondroitin sulfate proteoglycans, molecules that play a key role in development and plasticity during postnatal development and in the adult.
PNNs appear to be mainly present in the cortex, hippocampus, thalamus, brainstem, and the spinal cord. Studies of the rat brain have shown that the cortex contains high numbers of PNNs in the motor and primary sensory areas and relatively fewer in the association and limbic cortices. In the cortex, PNNs are associated mostly with inhibitory interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance in the adult brain.
History.
The existence of PNNs has been inferred by Golgi, Lugaro, Donaggio, Martinotti, Ramón y Cajal and Meyer. However, Ramón y Cajal credits Golgi with the discovery of PNNs because he was the first to draw attention to them and gave the first precise description in 1893. Moreover, Golgi brought interest to the subject due to his opinion that the PNN was not a neuronal structure but rather a "kind of corset of neurokeratin which impeded the spread of current from cell to cell". Despite debating the topic, Ramón y Cajal claimed that the perineuronal net was simply a staining artifact derived from the coagulation of extracellular fluids. Due to his influential opinion at the time, interest in the topic subsided.
Interest arose in the 1960s when several authors drew attention to the presence of periodic-acid-Schiff-positive (PAS-positive) material surrounding nerve cells. This PAS-positive material was suspected of being composed of negatively charged substances, such as chondroitin sulfate proteoglycans (CSPGs). However, the authors clung to the idea that the material was intricately connected to the blood–brain barrier and failed to see the similarities it had with the perineuronal net described by Golgi. Interest only rose again in the past few decades when it was discovered that PNNs constitute markers for physiologically mature neurons.
Composition.
PNNs are composed of a condensed matrix of chondroitin sulfate proteoglycans, molecules that consist of a core protein and a glycosaminoglycan (GAG) chain. The CS-GAG chains associated with PNNs differs from those found floating in the extra-cellular matrix in a noncondensed form. PNNs are composed of brevican, neurocan, versican, aggrecan, phosphacan, hyaluronan, tenascin-R and various link proteins. The CSPGs aggrecan, versican, neurocan, brevican, and phosphacan are bound to hyaluronan. Many of the components of PNNs are also expressed other forms of ECM in the brain. Aggrecan is selectively expressed in PNNs and is essential for the construction and maintenance of PNNs. PNNs found in both the brain and the spinal cord have the same composition. Chondroitinase ABC (ChABC), a bacterial enzyme routinely used to digest CSPGs, works by catalyzing the removal of the CS-GAG chains of CSPGs, thus it is not selective to PNNs. Mutant mice deficient in tenascin-R or link protein have attenuated PNNs,
In the cortex and other subcortical areas, PNNs preferentially surround GABAergic interneurons containing the calcium-binding protein parvalbumin. The onset of the critical period corresponds closely to the emergence of parvalbumin-positive cells. Parvalbumin-positive cells synapse onto α1-subunit-containing GABAA receptors. The α1-subunit-containing GABAA receptors have been shown to be the only GABAA receptors that drive cortical plasticity. For this reason, PNNs were first thought to have a strong role in the closure of the critical period.
Functions.
Neuroprotection.
A fine regulation of axonal and dendritic growth is required in the adult CNS to preserve important connections while still allowing for structural plasticity. This function has been recognized to be mediated by several myelin-associated proteins and CSPGs. In order to assess the physiological role of PNNs in the undamaged CNS, ChABC was injected in the healthy cerebellum of adult rats. In the site of ChABC injections, there was profuse outgrowth of the terminal branches of Purkinje cell neurons. However, myelinated axon segments were not affected and remained normal. Purkinje axon sprouting was first evident four days after the degradation of CSPGs. Within 42 days, the expression of CSPGs gradually recovered, at which point axon outgrowth regressed, indicating that there was no significant formation of stable synaptic contacts. While CSPGs are very important in neuroprotection, this indicates that CSPGs may not be the only molecules important for the preservation of anatomical plasticity.
Restriction of AMPA receptor mobility.
Cell surface proteins, including neurotransmitter receptors, are highly mobile in the plasma membrane due to lateral diffusion. Fast movements of AMPA-type glutamate receptors (AMPARs) are involved in the modulation of synaptic transmission. As a receptor is used, it becomes desensitized and unable to operate efficiently for a short period of time. Diffusion of the desensitized receptor for the exchange of a naive functional one increases synaptic fidelity during fast repetitive stimulation. PNNs compartmentalize the neuronal surface and act as lateral diffusion barriers for AMPARs, limiting synaptic exchange. This may be part of the reason that synaptic plasticity is limited once PNNs become upregulated.
Buffering system for cations.
Most of the parvalbumin-positive neurons surrounded by PNNs also contain the potassium channel Kv3.1b subunit. These specific cells have been identified as fast-spiking cells. These neurons have a low input resistance of the cell membrane, a high resting membrane potential, a short duration of both action potentials and the refractory period, a high firing frequency, and an almost constant amplitude of their action potentials. It appears that both Kv3.1 channels and PNNs are both required for the fast-spiking behavior of these neurons. These potassium channels are important because outward potassium currents are responsible for the repolarization of the cell membrane during an action potential. It has been shown that Kv3.1 currents allow a neuron to follow a high frequency stimulation and/or to generate high firing rates without spike adaption, characteristics that fit well with fast-spiking cells. This characteristic of the cells is important as blockade of the Kv3.1b channel has been shown to slow the rate of ocular dominance plasticity.
PNNs, with their strongly negative charge, may serve as cation exchangers preventing the free diffusion of potassium or sodium ions. Due to the spatial, temporal, and numerical disproportions between Na+ influx and K+ efflux, the PNN provides a possible buffering system for extracellular cations. However, this hypothesis has yet to be proven.
Role in neuroplasticity.
PNNs play an important role in neuroplasticity. Traumatic injury of the CNS results in degeneration of denervated and damaged neurons, the formation of a glial scar, and collateral sprouting of surviving neurons. PNNs have been shown to be inhibitory to axonal regeneration and outgrowth. CSPGs are the main axon growth inhibitory molecules in the glial scar that play a role in the failure of the axon to regenerate after injury. In the rat brain and spinal cord, the expression of various CSPGs (brevican, versican, neurocan, and NG2) increases after injury. "In vivo" treatment with ChABC results in the enhancement of the regeneration of axons (specifically dopaminergic neurons) and the promotion of axon regeneration and functional recovery following spinal cord injury.
CSPGs and PNNs are also implicated in the restricted plasticity present after CNS injury. In the rat cerebellum, application of ChABC promotes structural plasticity of Purkinje axons. Following spinal cord injury, rats treated with ChABC show structural and functional recovery in the form of increased regrowth of axons into the denervated territory and the recovery of motor and bladder function. Plasticity of intact areas in the brain stem and spinal cord also increases following spinal cord injury.
Ocular dominance plasticity.
The critical period is a stage when a necessary amount of experience is required for the proper organization of a neural pathway. The absence of this experience may lead to the permanent formation of incorrect connections. The classic model of the critical period has been the visual system. Normally, the primary visual cortex contains neurons organized in ocular dominance columns, with groups of neurons responding preferentially to one eye or the other. If an animal's dominant eye is sutured early in life and kept sutured through the visual critical period (monocular deprivation), the cortex permanently responds preferentially to the eye that was kept open, resulting in ocular dominance shift. However, if the eye is sutured after the critical period, the shift does not occur.
In rats, digestion of PNNs using the bacterial enzyme chondroitinase ABC reactivates the visual critical period. Specifically, digestion of PNNs in the visual cortex well after the closure of the critical period (postnatal day 70) reactivated critical period plasticity and allowed ocular dominance shift to occur. However, the effects of monocular deprivation in the reactivated case were not as strong as monocular deprivation during a normal critical period. Additionally, in adult rats that had been monocularly deprived since youth, digestion of PNNs brought about a full structural and functional recovery (recovery of ocular dominance, visual acuity, and dendritic spine density). However, this recovery only occurred once the open eye was sutured to allow the cortical representation of the deprived eye to recover.
Fear memories.
Fear conditioning in animals is used to model anxiety disorders such as PTSD. Fear conditioning works by pairing an initially neutral stimulus with an aversive stimulus, leading to long-lasting fear memories. In an adult animal, fear conditioning induces a permanent memory resilient to erasure by extinction. After extinction, conditioned fear responses can recover spontaneously after a reexposure to the aversive stimulus. In contrast, in early postnatal development, extinction of a conditioned fear response leads to memory erasure. The organization of PNNs in the amygdala coincides with this switch in fear memory resilience. In the adult animal, degradation of PNNs in the amygdala with ChABC renders subsequently acquired fear memories susceptible to erasure. Extinction training was necessary for the loss of fear behavior. Additionally, fear memories acquired before the degradation of the PNNs were not affected by their degradation.
Developmental song learning.
Developmental song learning is a model used for the sensorimotor critical period. Birdsong learning in the zebra finch occurs during a critical period similar to that for human speech. This critical period occurs in two parts. The first consists of an early perceptual phase in which sounds are merely memorized. This is followed by a second sensorimotor phase in which feedback is used to shape proper sounds. In the song nuclei HVC, over 80% of PNNs surround parvalbumin-positive neurons. The presence of perineuronal nets predicts the maturity of a zebra finch's song, with greater PNN density indicating a more mature song and likely greater synaptic stability. Unlike the visual critical period, extensive preliminary investigation has shown that degrading the PNNs with ChABC does not reopen the critical period of sensorimotor plasticity. This can be attributed to the additional complicating factors present in a sensorimotor system compared to a purely sensory system. In humans, complications in the speech sensorimotor critical period is implicated in disorders such as autism. Reopening of the critical period in zebra finches may lead to discoveries leading to treatment for these disorders.
Role in CNS pathology.
Epilepsy.
Epilepsy is a chronic neurological disorder characterized by abnormal electrical activity in the brain. This abnormal electrical activity results in increased plastic changes that play a part of the pathogenesis of the disease. Following seizures, there is a decrease in phosphacan and phosphacan-positive PNNs and an increase in cleaved brevican in the temporal lobe and hippocampus. Seizures also increase the amount of full-length neurocan, a CSPG only found in the neonatal brain. This degradation of CSPGs and PNNs could be responsible for the increased plasticity associated with the disorder.
Stroke.
Following stroke, there is some increased plasticity resulting in the restoration of some function. In the rat model, following a cortical lesion, there is a reduction of PNNs in the region surrounding the infarction. Specifically, there is a reduction in the CSPGs aggrecan, versican, and phosphacan and an accumulation of full-length neurocan. This downregulation of PNNs also occurs in brain regions as distant as the thalamus. The degradation of PNNs may be responsible for the increased plasticity seen post-stroke. One issue with typical stroke recovery is the typical period of increased plasticity is generally not long enough to allow stroke patients acceptable recovery of function. One possible treatment strategy may be to degrade PNNs for a longer period of time to allow for greater recovery.
Alzheimer's disease.
There appear to be several roles for CSPGs in Alzheimer's disease. PNNs may provide protection against excitotoxicity, oxidative stress, and the formation of neurofibrillary tangles. There have been conflicting reports as to the number of PNNs in the human Alzheimer's brain, with some studies reporting a reduction and others reporting no change. There is no clear consensus as the susceptibility of parvalbumin-positive neurons, the majority of neurons surrounded by PNNs. However, PNNs have been found to localize with both amyloid plaques and neurofibrillary tangles. Since amyloid plaques have been implicated in the progression of Alzheimer's disease, this suggests that PNNs are either instrumental in their formation or are a reaction to their formation. "In vitro" studies have shown that CSPGs promote beta amyloid fibril formation. Since beta amyloid is a strong stimulant to CSPG production and CSPGs are inhibitory to neuronal growth and synaptic plasticity, this may lead to the decreased axon density and synaptic loss in Alzheimer's disease.


Tom Webster (politician)

Thomas Stephen Webster, (born 5 July 1950) is a property valuer and former Labor Party local councillor and member of the New South Wales Legislative Assembly, representing the electorate of Wakehurst from 1978 to 1984.
Early years.
Born in 1950, Webster was educated at Rozelle Public School and Drummoyne Boys' High School (closed in 1990). After High school he attended Sydney Technical College and became a property valuer from 1970 for the Valuer-General's Department. As a Fellow of the Australian Property Institute (FAPI), Webster served as a divisional councillor from 2004 to 2009 and as president from 2006 to 2007.
Political career.
Webster joined the Grafton Branch of the Australian Labor Party in 1971 and joined the Dee Why branch in 1976, becoming President from 1977-1978. At age 28, he was pre-selected as Labor Party candidate for the NSW State seat of Wakehurst in 1978. The 1978 election saw a huge swing towards the Labor Party in NSW and was known as the 'Wranslide', in reference to the state leader, Neville Wran, with first-time seat wins in Wakehurst, Manly, Cronulla and Willoughby. Webster was elected on 7 October 1978, becoming the first Labor member of what was a traditionally safe Liberal seat, defeating the sitting Liberal member and Shadow Minister for Services, Allan Viney, on a swing of over 14 percent.
During his six years in Parliament, he served on a number of committees including the Public Accounts Committee. He was later appointed as senior policy adviser to the State Premier. He retained his seat at the 1981 election, gaining enough of a swing to technically make Wakehurst a safe Labor seat. However, he lost his seat to Liberal candidate John Booth at the 1984 election. With Booth only winning election on a margin of 1.6%, Wakehurst remained a marginal seat and Webster stood again as the Labor candidate at the 1988 election, but was again unsuccessful on a two-party-preferred result of 57-42% at an election that saw Labor lose power to the Coalition led by Nick Greiner.
Webster was later elected as a Councillor for B Riding (which became A Riding/Ward following the secession of Pittwater Council in 1992) on Warringah Shire Council in September 1991 and later served a single term as Deputy Mayor. He served on the Council until 1999 After leaving he returned to work exclusively for his Valuer Practice, T. S. Webster and Associates, which he had founded in 1988, but remains involved in the Dee Why Branch of the ALP. In the lead-up to the 2011 NSW state election, Webster was made a life member of the ALP and tried to mentor local Labor candidates but lamented to the Manly Daily that: "In my 40-year membership of the party I don’t think we have ever been in such dire straits", a comment that was reflected in the subsequent landslide defeat suffered by the party at that election.


Suctorial

Suctorial pertains to the adaptation for sucking or suction, as possessed by marine parasites such as the Cookiecutter shark, specifically in a specialised lip organ enabling attachment to the host.
Suctorial organs of a different form are possessed by the Solifugae arachnids, enabling the climbing of smooth, vertical surfaces.
Another variation on the suctorial organ can be found as part of the glossa proboscis of Masarinae (pollen wasps), enabling nectar feeding from the deep and narrow corolla of flowers.


American Neuropsychiatric Association

The American Neuropsychiatric Association (ANPA) is a non-profit organization of professionals in neuropsychiatry, behavioral neurology and the clinical neurosciences, with over 700 members from around the world. Established in 1988, its mission is to improve the lives of people with disorders at the interface of psychiatry and neurology, with the vision of transforming recognition, understanding and treatment of neuropsychiatric disorders. It founded in 1988 by two academic physicians doubly certified in neurology and psychiatry, Barry S. Fogel and Randolph Schiffer.
The ANPA holds an annual scientific meeting in the early spring. It has also established Special Interest Groups (SIGs) for its members to enhance peer discussion, education, and potential collaboration. Current SIGs include Clinical Practice, Conversion Disorders, Dementia, Developmental Disorders and Pediatrics, Early Career, Epilepsy, Forensics, Global Health, Movement Disorders, Neuroimaging and Traumatic Brain Injury.
Some other professional organizations with similar scope include the British Neuropsychiatry Association (BNPA), Royal College of Psychiatrists (UK) Section of Neuropsychiatry, the International Neuropsychiatric Association, and Neuropsychiatric forum (NPF).
Together with the Society for Behavioral and Cognitive Neurology, the ANPA co-sponsors the subspecialty certification in Behavioral Neurology & Neuropsychiatry, offered under the auspices of the United Council for Neurological Subspecialties (UCNS).
The "Journal of Neuropsychiatry and Clinical Neurosciences" (JNCN), published by the American Psychiatric Association, is the official journal of the ANPA.
Fellows of the ANPA (FANPA) are elected from members with special achievement in neuropsychiatry, behavioral neurology, neuropsychology or the clinical neurosciences. fellows include:
James R. Merikangas, M.D.
Barry S. Fogel, M.D.
Randolph B. Schiffer, M.D.
Gary J. Tucker, M.D.
Trevor R.P.Price, M.D.
Jeffrey L. Cummings, M.D.
Stephen Salloway, M.D., M.S.
Robert G. Robinson, M.D.
C. Edward Coffey, M.D
Stuart C. Yudofsky, M.D.
Thomas W. McAllister, M.D.
John J. Campbell, M.D.
Edward Lauterbach, M.D.
Jonathan M. Silver, M.D.
Robert A. Stern, Ph.D.
Paula T. Trzepacz, M.D.
Fred Ovsiew, M.D.
Laura A. Flashman, Ph.D.
Paul F. Malloy, Ph.D.
Richard M. Restak, M.D.
Sheldon Benjamin, M.D.
Robert C. Green, M.D.
Alya Reeve, M.D.
Nashaat Boutros, M.D.
James D. Duffy, M.B.Ch.B.
Robin A. Hurley, M.D.
David B. Arciniegas, M.D.
Daniel I. Kaufer, M.D.
Katherine H. Taber, Ph.D.
Kevin J. Black, M.D.
Allen J. Rubin, M.D.
Tiffany Chow, M.D.
Robert A. Bornstein, Ph.D.
Jeremy D. Schmahmann, M.D.
Yonas E. Geda, M.D.
Daniel R. Wilson, M.D., Ph.D.
Deborah N. Black, M.D.
Richard B. Ferrell, M.D.
Colin J. Harrington, M.D.
Bernardino Vaccaro, M.D.
Clark A. Anderson, M.D.
Miles G. Cunningham, M.D., Ph.D.
Mario F. Mendez, M.D., Ph.D.,
Kenneth Bryant, M.D.
W. Curt LaFrance, Jr., M.D., M.P.H.
Kristin Brousseau, D.O.
David A. Silbersweig, M.D.
Moises Gaviria, M.D.
Kaloyan S. Tanev, M.D.
Hal S. Wortzel, M.D.
Jay Salpekar, M.D.
Valerie Voon, M.D.
Omar Ghaffar, M.D., M.Sc., FRCPC
Margo D. Lauterbach, MD
Shirlene M. Sampson, M.D.
Vani Rao, M.B.B.S., M.D.
Andrea E. Cavanna, M.D., Ph.D., FRCP
Barbara Schildkrout, M.D.


Revival (theatre)

A revival is a restaging of a stage production after its original run has closed. New material may be added. A filmed version is said to be an adaptation and requires writing of a screenplay. Revivals are common in Broadway theatre.


Edward F. Fagan

Edward Francis Fagan (February 27, 1849 – December 7, 1901) was an American schoolteacher, principal, and politician from New York.
Life.
Fagan was born on February 27, 1849 in New York City, New York. He was of Irish parentage.
Fagan attended Manhattan College, graduating at the top of his class in 1869. He also received an M.A. in 1872 and a Ph.D. in 1880. He spent several years as a teacher for Manhattan College. In 1876, he moved to Maspeth, Queens. There, he was elected School Commissioner in 1882, served as the first principal of Long Island City High School for a number of years, and after the Consolidation of Greater New York he was appointed Superintendent of Schools in Queens. He held the latter position at the time of his death.
In 1885, Fagan was elected to the New York State Senate as a Democrat, representing New York's 1st State Senate district (Suffolk and Queens Counties). He served in the Senate in 1886 and 1887.
Fagan died at home from a brain abscess on December 7, 1901. He was buried in Calvary Cemetery.


The Tripods

The Tripods is a series of young adult novels written by John Christopher, beginning in 1967. The first two were the basis of a science fiction TV series, produced in the United Kingdom in the 1980s.
Synopsis.
The story of "The Tripods" is a variation on post-apocalyptic literature, wherein humanity has been enslaved by "Tripods" — gigantic three-legged walking machines, piloted by unseen alien entities (later identified as "Masters"). Human society is largely pastoral, with few habitations larger than villages, and what little industry exists is conducted under the watchful presence of the Tripods. Lifestyle is reminiscent of the Middle Ages, but small artifacts from the Modern Age are still used, such as watches.
Humans are controlled from the age of 14 by implants called "Caps," which suppress curiosity and creativity. Some people, whose minds are broken by the Caps, become vagrants. According to "The City of Gold and Lead", Masters begin to believe that humans should be capped at an earlier age "because some humans, in the year or two before they are Capped, become rebellious and act against the masters", but this cannot be done, because Capping must wait until the braincase has stopped growing.
Series.
"The White Mountains" (1967).
Life goes on largely as it had in the pre-industrial era, except that all adult humans are subject to Tripod control. Protagonist Will Parker, a thirteen-year-old boy living in the fictional English village of Wherton, is looking forward to being Capped at the next Capping Day, until a chance meeting with a mysterious fake-Capped man named Ozymandias prompts him to discover a world beyond the Tripods' control. He is accompanied by his cousin Henry and later by a French teenager named Jean-Paul Deliet, nicknamed "Beanpole." The novel climaxes with Henry and Beanpole discovering that earlier, when Will was captured by a Tripod, he was unknowingly implanted with a tracking device. When Henry and Beanpole remove the device, a nearby Tripod attacks them, but the boys defeat the Tripod and elude subsequent efforts to find them. The story ends with them joining the resistance, located in the eponymous White Mountains.
"" (1967).
After a year in the White Mountains, the resistance charges Will, Beanpole, and a German boy, Fritz, to infiltrate a Tripod city by competing in a regional sporting exhibition. Will, a boxer, and Fritz, a runner, win their respective contests, while Beanpole fails to win in the jumping events.
The winners are taken to the Tripod city in a pressurised dome astride a river. Inside the city, the boys encounter the Tripods' operators, whom they refer to as the "Masters." Human males are slaves inside the cities, while beautiful females are killed and preserved for the Masters to admire. Slaves are furnished with breathing masks to survive the aliens' atmosphere, but are rapidly exhausted by the stronger artificial gravity and must therefore be periodically replaced. The "gold" in the title refers to the city's color, while the "lead" refers to the heightened gravity.
Although Fritz is abused by his Master, Will is treated as a privileged pet by his. Eventually, Will's Master reveals a plan to replace the Earth's atmosphere with the Masters' toxic air to enable full control of the Earth. When the Master finds Will's diary, Will kills him to maintain the secret. With the assistance of Beanpole and Fritz, who temporarily stays behind to maintain Will’s alibi, he escapes and returns to the White Mountains with Beanpole. The story ends with Will and Beanpole giving Fritz up for dead and returning to the White Mountains, although he returns at the beginning of the next book.
"" (1968).
Will and Fritz travel to Eastern Europe, the Caucasus, and the Middle East to organize resistance against the Tripods. The resistance, having ambushed a Tripod and captured a Master, accidentally discover that alcohol has a strong soporific effect on them, and use this knowledge to simultaneously attack their cities. Having introduced alcohol into the aliens' city water systems, two raiding groups kill the Masters by forcing open airlocks and exposing the unconscious aliens to Earth's atmosphere; but the attack on the last city (located in Central America) fails. A secondary plan is undertaken using hot air balloons and newly developed bombs. The attack is initially unsuccessful, as the timers on the bombs cause them to detonate either before making contact with the dome of the city, or after the bomb has fallen clear. Henry jumps from his balloon onto the city's domed roof and holds the bomb in place, sacrificing himself and shattering the dome. Earth's atmosphere kills the Masters, and Henry is remembered as a hero.
Several years later, the Masters' atmosphere-seeding spaceship arrives and destroys the remains of their cities, then leaves – presumably since the cities contained "star maps" which showed the location of the Masters' home world, also to prevent the humans from reverse engineering their technology – although Beanpole notes that they have already learned much from the cities. Modern human technology, which was halted during the Masters' rule is rediscovered rapidly, including the theory of space travel.
The saga ends with the Resistance leader Julius being deposed at a summit of nations. As a result, the alliance built during the resistance falls apart, with nationalistic hostilities appearing and each country going their separate ways, in contrast to Julius' efforts to unite the world. Will, Beanpole, and Fritz reunite as a tribute to Julius, to work towards establishing a better world.
"" (1988).
"When the Tripods Came" is a prequel written twenty years after the publication of the original trilogy. The plot follows the description of the conquest given in "The City of Gold and Lead".
Fearing the technological potential of humanity, the so-called "Masters," unable to defeat humanity in a conventional war, hypnotise people through a television program called "The Trippy Show", later using temporary and finally permanent Caps to control them.
As in the original trilogy, the narrator of "When the Tripods Came" is a young English boy. He and a friend bear witness to a seemingly botched initial invasion by a single Tripod in the British countryside. After the event is old news, "The Trippy Show" begins broadcasting, and engenders in some viewers an enthusiasm that gradually becomes a mania. As an increasingly hypnotized society falls under the control of the Masters, he and his family escape to Guernsey by boat. When they find it is also controlled by the Capped, they hijack a plane to Switzerland, which has managed to restrict its hypnotized population better than other European nations. When the Swiss are eventually invaded and enslaved, the narrator and his family establish the "White Mountains" resistance movement of the original trilogy.
Editions.
Editions have been published by
The series has been translated into Arabic, Dutch, Danish, Finnish, French, German, Hebrew, Persian, Spanish, Greek, and Mandarin Chinese (Taiwan).
Comic books.
Multiple graphic adaptations have been produced, notably including:
Television series.
The television version of "The Tripods" was jointly produced by the BBC in the United Kingdom and the Seven Network in Australia. The music soundtrack was written by Ken Freeman. The series was noted for being one of the first to feature computer generated graphics and special effects.
Series one of "The Tripods", broadcast in 1984, which had 13 half-hour episodes written by the well-known author of many radio plays Alick Rowe, covers the first book, "The White Mountains"; the 12-episode second series (1985) covers "The City of Gold and Lead". Although a television script had been written for the third series, it never went into production.
The first series was released on both VHS and DVD. The BBC released "Tripods — The Complete Series 1 & 2" on DVD in March 2009.
Comparison with the novels.
When the BBC made the television series of The Tripods in the 1980s, they departed from Christopher's description of the Masters. In the television series, the Masters somewhat resemble the Tripods they drive. This makes the Tripods seem much more like mecha, similar to those described in "The War of the Worlds", than purely eccentric vehicles. In the BBC serial, the Masters did not need to eat, sleep or drink. Additionally, they were not the rulers of the city, but were, in turn, under the rule of beings made of pure energy, known as Cognoscs. The Masters came from a planet named Trion that was in the center of a triple star system.
The method by which the Masters name themselves is also different. Rather than having names, they are simply called by their addresses. Will's Master is called West Avenue 4, Sector 6, Level 8, or West 468.
The Masters in the BBC production did not breathe green air and did not prefer the high gravity and high temperature of those in the book, since these would have been extremely difficult or expensive to recreate onscreen at the time. Their treatment of the slaves, rather than being harsh and thoughtless, was reasonable to the point of being friendly, with luxuries provided for them.
To avoid an overuse of the mechanical Tripods, the producers invented a new faction, the "Black Guards," as a human police force with the task to enforce the will of the Masters. They served as a more immediate threat for Will, his friends and the resistance.


Visual cortex

The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and then reaches the visual cortex. The area of the visual cortex that receives the sensory input from the lateral geniculate nucleus is the primary visual cortex, also known as visual area 1 (V1), Brodmann area 17, or the striate cortex. The extrastriate areas consist of visual areas 2, 3, 4, and 5 (also known as V2, V3, V4, and V5, or Brodmann area 18 and all Brodmann area 19).
Both hemispheres of the brain include a visual cortex; the visual cortex in the left hemisphere receives signals from the right visual field, and the visual cortex in the right hemisphere receives signals from the left visual field.
Introduction.
The primary visual cortex (V1) is located in and around the calcarine fissure in the occipital lobe. Each hemisphere's V1 receives information directly from its ipsilateral lateral geniculate nucleus that receives signals from the contralateral visual hemifield.
Neurons in the visual cortex fire action potentials when visual stimuli appear within their receptive field. By definition, the receptive field is the region within the entire visual field that elicits an action potential. But, for any given neuron, it may respond best to a subset of stimuli within its receptive field. This property is called "neuronal tuning". In the earlier visual areas, neurons have simpler tuning. For example, a neuron in V1 may fire to any vertical stimulus in its receptive field. In the higher visual areas, neurons have complex tuning. For example, in the inferior temporal cortex (IT), a neuron may fire only when a certain face appears in its receptive field.
The visual cortex receives its blood supply primarily from the calcarine branch of the posterior cerebral artery.
Psychological model of the neural processing of visual information.
Ventral-dorsal model.
V1 transmits information to two primary pathways, called the ventral stream and the dorsal stream.
The what vs. where account of the ventral/dorsal pathways was first described by Ungerleider and Mishkin.
More recently, Goodale and Milner extended these ideas and suggested that the ventral stream is critical for visual perception whereas the dorsal stream mediates the visual control of skilled actions. It has been shown that visual illusions such as the Ebbinghaus illusion distort judgements of a perceptual nature, but when the subject responds with an action, such as grasping, no distortion occurs.
Work such as the one from Scharnowski and Gegenfurtner suggests that both the action and perception systems are equally fooled by such illusions. Other studies, however, provide strong support for the idea that skilled actions such as grasping are not affected by pictorial illusions and suggest that the action/perception dissociation is a useful way to characterize the functional division of labor between the dorsal and ventral visual pathways in the cerebral cortex.
Primary visual cortex (V1).
The primary visual cortex is the most studied visual area in the brain. In mammals, it is located in the posterior pole of the occipital lobe and is the simplest, earliest cortical visual area. It is highly specialized for processing information about static and moving objects and is excellent in pattern recognition.
The primary visual cortex, which is defined by its function or stage in the visual system, is approximately equivalent to the striate cortex, also known as Brodmann area 17, which is defined by its anatomical location. The name "striate cortex" is derived from the line of Gennari, a distinctive stripe visible to the naked eye that represents myelinated axons from the lateral geniculate body terminating in layer 4 of the gray matter.
The primary visual cortex is divided into six functionally distinct layers, labeled 1 to 6. Layer 4, which receives most visual input from the lateral geniculate nucleus (LGN), is further divided into 4 layers, labelled 4A, 4B, 4Cα, and 4Cβ. Sublamina 4Cα receives mostly magnocellular input from the LGN, while layer 4Cβ receives input from parvocellular pathways.
The average number of neurons in the adult human primary visual cortex in each hemisphere has been estimated at around 140 million.
Function.
The first stage of visual processing in the cortex is called V1.
V1 has a very well-defined map of the spatial information in vision. For example, in humans, the upper bank of the calcarine sulcus (in the occipital lobe) responds strongly to the lower half of visual field (below the center), and the lower bank of the calcarine to the upper half of visual field. In concept, this retinotopic mapping is a transformation of the visual image from retina to V1. The correspondence between a given location in V1 and in the subjective visual field is very precise: even the blind spots are mapped into V1. In terms of evolution, this correspondence is very basic and found in most animals that possess a V1. In humans and animals with a fovea (cones in the retina), a large portion of V1 is mapped to the small, central portion of visual field, a phenomenon known as cortical magnification. Perhaps for the purpose of accurate spatial encoding, neurons in V1 have the smallest receptive field size of any visual cortex microscopic regions.
The tuning properties of V1 neurons (what the neurons respond to) differ greatly over time. Early in time (40 ms and further) individual V1 neurons have strong tuning to a small set of stimuli. That is, the neuronal responses can discriminate small changes in visual orientations, spatial frequencies and colors. Furthermore, individual V1 neurons in humans and animals with binocular vision have ocular dominance, namely tuning to one of the two eyes. In V1, and primary sensory cortex in general, neurons with similar tuning properties tend to cluster together as cortical columns. David Hubel and Torsten Wiesel proposed the classic ice-cube organization model of cortical columns for two tuning properties: ocular dominance and orientation. However, this model cannot accommodate the color, spatial frequency and many other features to which neurons are tuned . The exact organization of all these cortical columns within V1 remains a hot topic of current research. The mathematical modeling of this function has been compared to Gabor transforms.
Later in time (after 100 ms), neurons in V1 are also sensitive to the more global organisation of the scene (Lamme & Roelfsema, 2000). These response properties probably stem from recurrent feedback processing (the influence of higher-tier cortical areas on lower-tier cortical areas) and lateral connections from pyramidal neurons (Hupe et al. 1998). While feedforward connections are mainly driving, feedback connections are mostly modulatory in their effects (Angelucci et al., 2003; Hupe et al., 2001). Evidence shows that feedback originating in higher-level areas such as V4, IT, or MT, with bigger and more complex receptive fields, can modify and shape V1 responses, accounting for contextual or extra-classical receptive field effects (Guo et al., 2007; Huang et al., 2007; Sillito et al., 2006).
The visual information relayed to V1 is not coded in terms of spatial (or optical) imagery but rather are better described as edge detection. As an example, for an image comprising half side black and half side white, the dividing line between black and white has strongest local contrast (that is, edge detection) and is encoded, while few neurons code the brightness information (black or white per se). As information is further relayed to subsequent visual areas, it is coded as increasingly non-local frequency/phase signals. Note that, at these early stages of cortical visual processing, spatial location of visual information is well preserved amid the local contrast encoding (edge detection).
A theoretical explanation of the computational function of the simple cells in the primary visual cortex has been presented in. It is described how receptive field shapes similar to those found by the biological receptive field measurements performed by DeAngelis et al. can be derived as a consequence of structural properties of the environment in combination with internal consistency requirements to guarantee consistent image representations over multiple spatial and temporal scales. It is also described how the characteristic receptive field shapes, tuned to different scales, orientations and directions in image space, allow the visual system to compute invariant responses under natural image transformations at higher levels in the visual hierarchy.
In primates, one role of V1 might be to create a saliency map (highlights what is important) from visual inputs to guide the shifts of attention known as gaze shifts.
It could do so by transforming visual inputs to neural firing rates from millions of neurons, such that the visual location signaled by the highest firing neuron is the most salient location to attract gaze shift. V1's outputs are received by the superior colliculus (in the mid-brain), among other locations, which reads out the V1 activities to guide gaze shifts.
Differences in size of V1 also seem to have an effect on the perception of illusions.
V2.
Visual area V2, or secondary visual cortex, also called prestriate cortex, is the second major area in the visual cortex, and the first region within the visual association area. It receives strong feedforward connections from V1 (direct and via the pulvinar) and sends strong connections to V3, V4, and V5. It also sends strong feedback connections to V1.
In terms of anatomy, V2 is split into four quadrants, a dorsal and ventral representation in the left and the right hemispheres. Together, these four regions provide a complete map of the visual world. V2 has many properties in common with V1: Cells are tuned to simple properties such as orientation, spatial frequency, and color. The responses of many V2 neurons are also modulated by more complex properties, such as the orientation of illusory contours, binocular disparity, and whether the stimulus is part of the figure or the ground. Recent research has shown that V2 cells show a small amount of attentional modulation (more than V1, less than V4), are tuned for moderately complex patterns, and may be driven by multiple orientations at different subregions within a single receptive field.
It is argued that the entire ventral visual-to-hippocampal stream is important for visual memory. This theory, unlike the dominant one, predicts that object-recognition memory (ORM) alterations could result from the manipulation in V2, an area that is highly interconnected within the ventral stream of visual cortices. In the monkey brain, this area receives strong feedforward connections from the primary visual cortex (V1) and sends strong projections to other secondary visual cortices (V3, V4, and V5). Most of the neurons of this area in primates are tuned to simple visual characteristics such as orientation, spatial frequency, size, color, and shape. Anatomical studies implicate layer 3 of area V2 in visual-information processing. In contrast to layer 3, layer 6 of the visual cortex is composed of many types of neurons, and their response to visual stimuli is more complex.
In one study, the Layer 6 cells of the V2 cortex were found to play a very important role in the storage of Object Recognition Memory as well as the conversion of short-term object memories into long-term memories.
Third visual cortex, including area V3.
The term third visual complex refers to the region of cortex located immediately in front of V2, which includes the region named visual area V3 in humans. The "complex" nomenclature is justified by the fact that some controversy still exists regarding the exact extent of area V3, with some researchers proposing that the cortex located in front of V2 may include two or three functional subdivisions. For example, David Van Essen and others (1986) have proposed the existence of a "dorsal V3" in the upper part of the cerebral hemisphere, which is distinct from the "ventral V3" (or ventral posterior area, VP) located in the lower part of the brain. Dorsal and ventral V3 have distinct connections with other parts of the brain, appear different in sections stained with a variety of methods, and contain neurons that respond to different combinations of visual stimulus (for example, colour-selective neurons are more common in the ventral V3). Additional subdivisions, including V3A and V3B have also been reported in humans. These subdivisions are located near dorsal V3, but do not adjoin V2.
Dorsal V3 is normally considered to be part of the dorsal stream, receiving inputs from V2 and from the primary visual area and projecting to the posterior parietal cortex. It may be anatomically located in Brodmann area 19. Braddick using fMRI has suggested that area V3/V3A may play a role in the processing of global motion Other studies prefer to consider dorsal V3 as part of a larger area, named the dorsomedial area (DM), which contains a representation of the entire visual field. Neurons in area DM respond to coherent motion of large patterns covering extensive portions of the visual field (Lui and collaborators, 2006).
Ventral V3 (VP), has much weaker connections from the primary visual area, and stronger connections with the inferior temporal cortex. While earlier studies proposed that VP contained a representation of only the upper part of the visual field (above the point of fixation), more recent work indicates that this area is more extensive than previously appreciated, and like other visual areas it may contain a complete visual representation. The revised, more extensive VP is referred to as the ventrolateral posterior area (VLP) by Rosa and Tweedale.
V4.
Visual area V4 is one of the visual areas in the extrastriate visual cortex. In macaques, it is located anterior to V2 and posterior to posterior inferotemporal area (PIT). It comprises at least four regions (left and right V4d, left and right V4v), and some groups report that it contains rostral and caudal subdivisions as well. It is unknown whether the human V4 is as expansive as that of the macaque homologue which is a subject of debate.
V4 is the third cortical area in the ventral stream, receiving strong feedforward input from V2 and sending strong connections to the PIT. It also receives direct input from V1, especially for central space. In addition, it has weaker connections to V5 and dorsal prelunate gyrus (DP).
V4 is the first area in the ventral stream to show strong attentional modulation. Most studies indicate that selective attention can change firing rates in V4 by about 20%. A seminal paper by Moran and Desimone characterizing these effects was the first paper to find attention effects anywhere in the visual cortex.
Like V2, V4 is tuned for orientation, spatial frequency, and color. Unlike V2, V4 is tuned for object features of intermediate complexity, like simple geometric shapes, although no one has developed a full parametric description of the tuning space for V4. Visual area V4 is not tuned for complex objects such as faces, as areas in the inferotemporal cortex are.
The firing properties of V4 were first described by Semir Zeki in the late 1970s, who also named the area. Before that, V4 was known by its anatomical description, the prelunate gyrus. Originally, Zeki argued that the purpose of V4 was to process color information. Work in the early 1980s proved that V4 was as directly involved in form recognition as earlier cortical areas. This research supported the two-streams hypothesis, first presented by Ungerleider and Mishkin in 1982.
Recent work has shown that V4 exhibits long-term plasticity, encodes stimulus salience, is gated by signals coming from the frontal eye fields, and shows changes in the spatial profile of its receptive fields with attention.
Middle temporal visual area (V5).
The middle temporal visual area (MT or V5) is a region of extrastriate visual cortex. In several species of both New World monkeys and Old World monkeys the MT area contains a high concentration of direction-selective neurons. The MT in primates is thought to play a major role in the perception of motion, the integration of local motion signals into global percepts, and the guidance of some eye movements.
Connections.
MT is connected to a wide array of cortical and subcortical brain areas. Its input comes from visual cortical areas V1, V2 and dorsal V3 (dorsomedial area), the koniocellular regions of the LGN, and the inferior pulvinar. The pattern of projections to MT changes somewhat between the representations of the foveal and peripheral visual fields, with the latter receiving inputs from areas located in the midline cortex and retrosplenial region.
A standard view is that V1 provides the "most important" input to MT. Nonetheless, several studies have demonstrated that neurons in MT are capable of responding to visual information, often in a direction-selective manner, even after V1 has been destroyed or inactivated. Moreover, research by Semir Zeki and collaborators has suggested that certain types of visual information may reach MT before it even reaches V1.
MT sends its major output to areas located in the cortex immediately surrounding it, including areas FST, MST, and V4t (middle temporal crescent). Other projections of MT target the eye movement-related areas of the frontal and parietal lobes (frontal eye field and lateral intraparietal area).
Function.
The first studies of the electrophysiological properties of neurons in MT showed that a large portion of the cells are tuned to the speed and direction of moving visual stimuli.
Lesion studies have also supported the role of MT in motion perception and eye movements. Neuropsychological studies of a patient unable to see motion, seeing the world in a series of static 'frames' instead, suggested that V5 in the primate is homologous to MT in the human.
However, since neurons in V1 are also tuned to the direction and speed of motion, these early results left open the question of precisely what MT could do that V1 could not. Much work has been carried out on this region, as it appears to integrate local visual motion signals into the global motion of complex objects.
For example, "lesion" to the V5 leads to deficits in perceiving motion and processing of complex stimuli. It contains many neurons selective for the motion of complex visual features (line ends, corners). "Microstimulation" of a neuron located in the V5 affects the perception of motion. For example, if one finds a neuron with preference for upward motion in a monkey's V5 and stimulates it with an electrode, then the monkey becomes more likely to report 'upward' motion when presented with stimuli containing 'left' and 'right' as well as 'upward' components.
There is still much controversy over the exact form of the computations carried out in area MT and some research suggests that feature motion is in fact already available at lower levels of the visual system such as V1.
Functional organization.
MT was shown to be organized in direction columns. DeAngelis argued that MT neurons were also organized based on their tuning for binocular disparity.
V6.
The dorsomedial area (DM) also known as V6, appears to respond to visual stimuli associated with self-motion and wide-field stimulation. V6 is a subdivision of the visual cortex of primates first described by John Allman and Jon Kaas in 1975. V6 is located in the dorsal part of the extrastriate cortex, near the deep groove through the centre of the brain (medial longitudinal fissure), and typically also includes portions of the medial cortex, such as the parieto-occipital sulcus (POS). DM contains a topographically organized representation of the entire field of vision.
There are similarities between the visual area V5 and V6 of the common marmoset. Both areas receive direct connections from the primary visual cortex. And both have a high myelin content, a characteristic that is usually present in brain structures involved in fast transmission of information.
For many years, it was considered that DM only existed in New World monkeys. However, more recent research has suggested that DM also exists in Old World monkeys and humans. V6 is also sometimes referred to as the parieto-occipital area (PO), although the correspondence is not exact.
Properties.
Neurons in area DM/V6 of night monkeys and common marmosets have unique response properties, including an extremely sharp selectivity for the orientation of visual contours, and preference for long, uninterrupted lines covering large parts of the visual field.
However, in comparison with area MT, a much smaller proportion of DM cells shows selectivity for the direction of motion of visual patterns. Another notable difference with area MT is that cells in DM are attuned to low spatial frequency components of an image, and respond poorly to the motion of textured patterns such as a field of random dots. These response properties suggest that DM and MT may work in parallel, with the former analyzing self-motion relative to the environment, and the latter analyzing the motion of individual objects relative to the background.
Recently, an area responsive to wide-angle flow fields has been identified in the human and is thought to be a homologue of macaque area V6.
Pathways.
The connections and response properties of cells in DM/ V6 suggest that this area is a key node in a subset of the 'dorsal stream', referred to by some as the 'dorsomedial pathway'. This pathway is likely to be important for the control of skeletomotor activity, including postural reactions and reaching movements towards objects The main 'feedforward' connection of DM is to the cortex immediately rostral to it, in the interface between the occipital and parietal lobes (V6A). This region has, in turn, relatively direct connections with the regions of the frontal lobe that control arm movements, including the premotor cortex.


Bebe Moore Campbell

Bebe Moore Campbell (February 18, 1950 – November 27, 2006), was an American author, journalist and teacher. Campbell was the author of three "New York Times" bestsellers: "Brothers and Sisters", "Singing in the Comeback Choir", and "What You Owe Me", which was also a "Los Angeles Times" "Best Book of 2001". Her other works include the novel "Your Blues Ain't Like Mine", which was a "New York Times" Notable Book of the Year and the winner of the NAACP Image Award for Literature; her memoir, "Sweet Summer: Growing Up With and Without My Dad"; and her first nonfiction book, "Successful Women, Angry Men: Backlash in the Two-Career Marriage". Her essays, articles, and excerpts appear in many anthologies.
Early life and education.
Born Elizabeth Bebe Moore, an only child, and reared in Philadelphia, Pennsylvania, she graduated from the Philadelphia High School for Girls and earned a Bachelor of Science degree in elementary education from the University of Pittsburgh. She was an honorary member of Alpha Kappa Alpha sorority.
Career.
Campbell's works of fiction would often relay the harmful impact that racism would inflict on individuals and their relationships. In 1992 Campbell's would release her first, and most critically acclaimed novel, "Your Blues Ain't Like Mine", which was described as one of the most influential books of 1992 by "The New York Times Magazine". This book, which was inspired by the murder of Emmett Till in 1955, describes the impacts of this senseless crime experienced by the victim's family. Campbell, inspired by the Rodney King beating and the subsequent Los Angeles riots, wrote her second novel titled, "Brothers and Sister". This novel would be named as a "The New York Times Magazine" best seller just two weeks after its release in 1994.
Campbell's interest in mental health was the catalyst for her first children's book, "Sometimes My Mommy Gets Angry", which was published in September 2003. This book won the National Alliance on Mental Illness (NAMI) Outstanding Literature Award for 2003. The book tells the story of how a little girl copes with being reared by her mentally ill mother. Ms. Campbell was a member of the National Alliance for the Mentally Ill and a founding member of NAMI-Inglewood. Her book "72 Hour Hold" also deals with mental illness. Her first play, "Even with the Madness", debuted in New York City in June 2003. This work revisited the theme of mental illness and the family. As a journalist, Campbell wrote articles for "The New York Times Magazine", "The Washington Post", the "Los Angeles Times", "Essence", "Ebony", "Black Enterprise", as well as other publications. She was a regular commentator for "Morning Edition" a program on National Public Radio.
Personal life and death.
Campbell lived in Los Angeles, California, with her husband, Ellis Gordon Jr.; they raised two children, a son, Ellis Gordon III, and a daughter, actress Maia Campbell, from Campbell's previous marriage to Tiko Campbell. Maia Campbell is best known for her role as "Tiffany" on "In the House." Bebe Moore Campbell died from brain cancer, aged 56, on November 27, 2006, and was interred at Inglewood Park Cemetery, Inglewood, California. Her favorite quote on being a writer was: "Discipline is the servant of inspiration."
Campbell's personal archives are housed in the Bebe Moore Campbell collection at the University of Pittsburgh Archives Service Center.


Furostilbestrol

Furostilbestrol (INN), also known as diethylstilbestrol di(2-furoate) or simply as diesthylstilbestrol difuroate, is a synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol that was never marketed. It is an ester of diethylstilbestrol and was described in the literature in 1952.


Combined injectable birth control

Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy.
CICs are different from progestogen-only injectable contraceptives (POICs), such as depot medroxyprogesterone acetate (DMPA; brand names Depo-Provera, Depo-SubQ Provera 104) and norethisterone enantate (NETE; brand name Noristerat), which are not combined with an estrogen and are given once every two to three months instead of once a month.
Hormonal contraception works primarily by preventing ovulation, but it may also thicken the cervical mucus inhibiting sperm penetration. Hormonal contraceptives also have effects on the endometrium, that theoretically could affect implantation.
Medical uses.
CICs are administered by intramuscular injection into the deltoid, gluteus maximus, or anterior thigh. They are ideally administered every 28 to 30 days, though they have been demonstrated to be effective up to 33 days.
Some CICs have been said to be used by transgender women as a means of feminizing hormone therapy as well.
Available forms.
A variety of different CICs, generally containing a short-acting natural estradiol ester and a long-acting progestin ester, are available for clinical use. Estrogens that are used include estradiol valerate, estradiol cypionate, estradiol enantate, estradiol benzoate butyrate, and estradiol, while progestins that are used include norethisterone enantate, medroxyprogesterone acetate, algestone acetophenide (dihydroxyprogesterone acetophenide), hydroxyprogesterone caproate, and megestrol acetate. Estradiol benzoate has a duration that is too short for once-monthly CICs, and is not used in them. Conversely, estradiol enantate is said to have a duration that is too long for once-monthly CICs, but is nonetheless used in them.
Side effects.
Side effects of CICs, besides menstrual bleeding changes, are minimal. The most prominent side effects of CICs are menstrual irregularities during the first 3 to 6 months of use. Dysmenorrhea has been reported in 30 to 65% of women. Other side effects include breast tenderness/pain, headache, and libido changes. Some fluid retention can occur, but weight gain is minimal. Local injection site reactions have also been reported in 15 to 35% of women.
Effects of CICs on coagulation and fibrinolysis are minimal and are not thought to be clinically relevant. Conversely, combined oral contraceptive pills containing ethinylestradiol have considerable effects on coagulation and fibrinolysis. The differences can be attributed to the lack of the first-pass effect with parenteral administration as well as structural and pharmacological differences between estradiol and ethinylestradiol.
Pharmacology.
CICs contain an estrogen and a progestin. The estrogen is generally a short-acting estradiol ester, which acts as a prodrug of estradiol. Esters of estradiol are natural and bioidentical estrogens, and are believed to have more favorable effects on lipid metabolism, cardiovascular health, and hemostasis than synthetic estrogens such as ethinylestradiol. The progestin is a long-acting progestogen ester, which may or may not act as a prodrug. Progesterone derivatives including medroxyprogesterone acetate, algestone acetophenide (dihydroxyprogesterone acetophenide), hydroxyprogesterone caproate, and megestrol acetate are active themselves and are not prodrugs, whereas the testosterone derivative norethisterone enantate is a prodrug of norethisterone. Regardless of whether they are prodrugs or not, steroid esters form a depot and have an extended duration of action due to a depot effect when administered by intramuscular or subcutaneous injection.
Because CICs are administered parenterally, they bypass the first-pass effect in the liver and intestines that occurs with oral administration of estrogens. However, is estimated that about 20% of an administered dose does still eventually pass through the liver. Hence, these preparations are not completely liver-neutral. Nonetheless, they have dramatically reduced hepatic effects relative to oral ethinylestradiol. In addition, parenteral estradiol in general has about 4- or 5-fold reduced potency in the liver than oral estradiol.
History.
The first CIC to be studied was estradiol valerate/hydroxyprogesterone caproate (EV/OHPC) in 1963, and the second CIC to be studied was estradiol enantate/algestone acetophenide (E2-EN/DHPA) in 1964. In 1967, E2-EN/DHPA was in the late stages of clinical development. By 1969, the medication was available for medical use under the brand name Perlutal. Within a few years, it was marketed under other brand names such as Topasel and Ova-Repos as well. In addition, several other CICs had been introduced for medical use by 1972. By 1976, two major CICs were in use: E2-EN/DHPA (brand names Perlutan, Topasel) in Spain and Latin America, and EV/OHPC (brand name Injectable No. 1) in China. These CICs have been described as first-generation CICs. Two second-generation CICs, estradiol cypionate/medroxyprogesterone acetate (EC/MPA; brand names Cyclofem and later Lunelle) and estradiol valerate/norethisterone enantate (EV/NETE; brand name Mesigyna), were introduced for clinical use in 1993. On 5 October 2000, Pharmacia received FDA approval for Lunelle Monthly Contraceptive Injection. In April 2003, Pharmacia was acquired by Pfizer (makers of depot medroxyprogesterone acetate). In October 2003, Lunelle was discontinued in the United States.
Society and culture.
Availability.
CICs are available in many countries throughout the world, including widely throughout Central and South America, in Mexico and the Caribbean, in China, in several Southeast Asian and African countries, and in Turkey. They were also previously available in the United States, Portugal, and Spain, but have been discontinued in these countries.
Research.
Many other CICs have been studied but have not been approved or marketed for clinical use.
The following are marketed CICs at different doses than those that are approved:
The half-progestin-dose formulation of estradiol valerate/norethisterone enantate (5 mg / 25 mg) is also known as HRP-103 and the half-progestin-dose formulation of estradiol cypionate/medroxyprogesterone acetate (5 mg / 12.5 mg) is also known as HRP-113.
The following are CICs that have never been marketed:


Cerebellar tentorium

The cerebellar tentorium or tentorium cerebelli (Latin for "tent of the cerebellum") is an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes.
Structure.
The cerebellar tentorium is an arched lamina, elevated in the middle, and inclining downward toward the circumference.
It covers the top of the cerebellum, and supports the occipital lobes of the brain.
Its anterior border is free and concave, and bounds a large oval opening, the tentorial incisure, through which pass the cerebral peduncles.
It is attached, behind, by its convex border, to the transverse ridges upon the inner surface of the occipital bone, and there encloses the transverse sinuses; in front, to the superior angle of the petrous part of the temporal bone on either side, enclosing the superior petrosal sinuses.
At the apex of the petrous part of the temporal bone the free and attached borders meet, and, crossing one another, are continued forward to be fixed to the anterior and posterior clinoid processes (respectively) of the sphenoid bone.
To the middle line of its upper surface the posterior border of the falx cerebri is attached, the straight sinus being placed at their line of junction.
Clinical significance.
Brain tumors are often characterized as supratentorial (above the tentorium) and infratentorial (below the tentorium). The location of the tumor can help in determining the type of tumor, as different tumors occur with different frequencies at each location. Additionally, most childhood primary brain tumors are infratentorial, while most adult primary brain tumors are supratentorial. The location of the tumor may have prognostic significance as well.
Since the tentorium is a hard structure, if there is an expansion of the volume of the brain or its surrounding matter above the tentorium, such as because of a tumour or bleeding, the brain can get pushed down partly through the tentorium. This is called herniation and will often cause an enlarged pupil on the affected side, due to pressure on the oculomotor nerve. Tentorial herniation is a serious symptom, especially since the brainstem is likely to be compressed as well if the intracranial pressure rises further. A common type of herniation is uncal herniation.
Calcifications within the cerebellar tentorium are relatively common in elderly people; they seem to rarely cause symptoms.


Cerebral cortex

The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just ten per cent consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness.
In most mammals, apart from small mammals that have small brains, the cerebral cortex is folded, providing a greater surface area in the confined volume of the cranium. Apart from minimising brain and cranial volume, cortical folding is crucial for the wiring of the brain and its functional organisation. In mammals with a small brain there is no folding and the cortex is smooth.
A fold or ridge in the cortex is termed a gyrus (plural gyri) and a groove is termed a sulcus (plural sulci). These surface convolutions appear during fetal development and continue to mature after birth through the process of gyrification. In the human brain the majority of the cerebral cortex is not visible from the outside, but buried in the sulci, and the insular cortex is completely hidden. The major sulci and gyri mark the divisions of the cerebrum into the lobes of the brain.
There are between 14 and 16 billion neurons in the human cerebral cortex. These are organised into horizontal layers, and radially into cortical columns and minicolumns. Cortical areas have specific functions such as movement in the motor cortex, and sight in the visual cortex.
Structure.
The cerebral cortex is the outer covering of the surfaces of the cerebral hemispheres and is folded into peaks called gyri, and grooves called sulci. In the human brain it is between two and three or four millimetres thick, and makes up 40 per cent of the brain's mass. 90 per cent of the cerebral cortex is the six-layered neocortex with the other 10 per cent made up of allocortex. There are between 14 and 16 billion neurons in the cortex, and these are organized radially in cortical columns, and minicolumns, in the horizontally organized layers of the cortex.
The neocortex is separable into different regions of cortex known in the plural as cortices, and include the motor cortex and visual cortex. About two thirds of the cortical surface is buried in the sulci and the insular cortex is completely hidden. The cortex is thickest over the top of a gyrus and thinnest at the bottom of a sulcus.
Folds.
The cerebral cortex is folded in a way that allows a large surface area of neural tissue to fit within the confines of the neurocranium. When unfolded in the human, each hemispheric cortex has a total surface area of about . The folding is inward away from the surface of the brain, and is also present on the medial surface of each hemisphere within the longitudinal fissure. Most mammals have a cerebral cortex that is convoluted with the peaks known as gyri and the troughs or grooves known as sulci. Some small mammals including some small rodents have smooth cerebral surfaces without gyrification.
Lobes.
The larger sulci and gyri mark the divisions of the cortex of the cerebrum into the lobes of the brain. There are four main lobes: the frontal lobe, parietal lobe, temporal lobe, and occipital lobe. The insular cortex is often included as the insular lobe. The limbic lobe is a rim of cortex on the medial side of each hemisphere and is also often included. There are also three lobules of the brain described: the paracentral lobule, the superior parietal lobule, and the inferior parietal lobule.
Thickness.
For species of mammals, larger brains (in absolute terms, not just in relation to body size) tend to have thicker cortices. The smallest mammals, such as shrews, have a neocortical thickness of about 0.5 mm; the ones with the largest brains, such as humans and fin whales, have thicknesses of 2–4 mm. There is an approximately logarithmic relationship between brain weight and cortical thickness.
Magnetic resonance imaging of the brain (MRI) makes it possible to get a measure for the thickness of the human cerebral cortex and relate it to other measures. The thickness of different cortical areas varies but in general, sensory cortex is thinner than motor cortex. One study has found some positive association between the cortical thickness and intelligence.
Another study has found that the somatosensory cortex is thicker in migraine sufferers, though it is not known if this is the result of migraine attacks or the cause of them.
A later study using a larger patient population reports no change in the cortical thickness in migraine sufferers.
A genetic disorder of the cerebral cortex, whereby decreased folding in certain areas results in a microgyrus, where there are four layers instead of six, is in some instances seen to be related to dyslexia.
Layers of neocortex.
The neocortex is formed of six layers, numbered I to VI, from the outermost layer I – near to the pia mater, to the innermost layer VI – near to the underlying white matter. Each cortical layer has a characteristic distribution of different neurons and their connections with other cortical and subcortical regions. There are direct connections between different cortical areas and indirect connections via the thalamus.
One of the clearest examples of cortical layering is the line of Gennari in the primary visual cortex. This is a band of whiter tissue that can be observed with the naked eye in the calcarine sulcus of the occipital lobe. The line of Gennari is composed of axons bringing visual information from the thalamus into layer IV of the visual cortex.
Staining cross-sections of the cortex to reveal the position of neuronal cell bodies and the intracortical axon tracts allowed neuroanatomists in the early 20th century to produce a detailed description of the "laminar structure of the cortex" in different species. The work of Korbinian Brodmann (1909) established that the mammalian neocortex is consistently divided into six layers.
Layer I.
Layer I is the molecular layer, and contains few scattered neurons, including GABAergic rosehip neurons. Layer I consists largely of extensions of apical dendritic tufts of pyramidal neurons and horizontally oriented axons, as well as glial cells. During development, Cajal-Retzius cells and subpial granular layer cells are present in this layer. Also, some spiny stellate cells can be found here. Inputs to the apical tufts are thought to be crucial for the "feedback" interactions in the cerebral cortex involved in associative learning and attention. While it was once thought that the input to layer I came from the cortex itself, it is now realized that layer I across the cerebral cortex mantle receives substantial input from "matrix" or M-type thalamus cells (in contrast to "core" or C-type that go to layer IV).
Layer II.
Layer II, the external granular layer, contains small pyramidal neurons and numerous stellate neurons.
Layer III.
Layer III, the external pyramidal layer, contains predominantly small and medium-size pyramidal neurons, as well as non-pyramidal neurons with vertically oriented intracortical axons; layers I through III are the main target of interhemispheric corticocortical afferents, and layer III is the principal source of corticocortical efferents.
Layer IV.
Layer IV, the internal granular layer, contains different types of stellate and pyramidal cells, and is the main target of thalamocortical afferents from thalamus type C neurons (core-type ) as well as intra-hemispheric corticocortical afferents. The layers above layer IV are also referred to as supragranular layers (layers I-III), whereas the layers below are referred to as infragranular layers (layers V and VI).
Layer V.
Layer V, the internal pyramidal layer, contains large pyramidal neurons. Axons from these leave the cortex and connect with subcortical structures including the basal ganglia. In the primary motor cortex of the frontal lobe, layer V contains giant pyramidal cells called Betz cells, whose axons travel through the internal capsule, the brain stem, and the spinal cord forming the corticospinal tract, which is the main pathway for voluntary motor control.
Layer VI.
Layer VI, the polymorphic or multiform layer, contains few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons; layer VI sends efferent fibers to the thalamus, establishing a very precise reciprocal interconnection between the cortex and the thalamus. That is, layer VI neurons from one cortical column connect with thalamus neurons that provide input to the same cortical column. These connections are both excitatory and inhibitory. Neurons send excitatory fibers to neurons in the thalamus and also send collaterals to the thalamic reticular nucleus that inhibit these same thalamus neurons or ones adjacent to them. One theory is that because the inhibitory output is reduced by cholinergic input to the cerebral cortex, this provides the brainstem with adjustable "gain control for the relay of lemniscal inputs".
Columns.
The cortical layers are not simply stacked one over the other; there exist characteristic connections between different layers and neuronal types, which span all the thickness of the cortex. These cortical microcircuits are grouped into cortical columns and minicolumns. It has been proposed that the minicolumns are the basic functional units of the cortex. In 1957, Vernon Mountcastle showed that the functional properties of the cortex change abruptly between laterally adjacent points; however, they are continuous in the direction perpendicular to the surface. Later works have provided evidence of the presence of functionally distinct cortical columns in the visual cortex (Hubel and Wiesel, 1959), auditory cortex,
and associative cortex.
Cortical areas that lack a layer IV are called agranular. Cortical areas that have only a rudimentary layer IV are called dysgranular. Information processing within each layer is determined by different temporal dynamics with that in layers II/III having a slow 2 Hz oscillation while that in layer V has a fast 10–15 Hz oscillation.
Types of cortex.
Based on the differences in laminar organization the cerebral cortex can be classified into two types, the large area of neocortex which has six cell layers, and the much smaller area of allocortex that has three or four layers:
There is a transitional area between the neocortex and the allocortex called the paralimbic cortex, where layers 2, 3 and 4 are merged. This area incorporates the proisocortex of the neocortex and the periallocortex of the allocortex. In addition, the cerebral cortex may be classified into four lobes: the frontal lobe, temporal lobe, the parietal lobe, and the occipital lobe, named from their overlying bones of the skull.
Blood supply and drainage.
Blood supply to the cerebral cortex is part of the cerebral circulation. Cerebral arteries supply the blood that perfuses the cerebrum. This arterial blood carries oxygen, glucose, and other nutrients to the cortex. Cerebral veins drain the deoxygenated blood, and metabolic wastes including carbon dioxide, back to the heart.
The main arteries supplying the cortex are the anterior cerebral artery, the middle cerebral artery, and the posterior cerebral artery. The anterior cerebral artery supplies the anterior portions of the brain, including most of the frontal lobe. The middle cerebral artery supplies the parietal lobes, temporal lobes, and parts of the occipital lobes. The middle cerebral artery splits into two branches to supply the left and right hemisphere, where they branch further. The posterior cerebral artery supplies the occipital lobes.
The circle of Willis is the main blood system that deals with blood supply in the cerebrum and cerebral cortex.
Development.
The prenatal development of the cerebral cortex is a complex and finely tuned process called corticogenesis, influenced by the interplay between genes and the environment.
Neural tube.
The cerebral cortex develops from the most anterior part, the forebrain region, of the neural tube. The neural plate folds and closes to form the neural tube. From the cavity inside the neural tube develops the ventricular system, and, from the neuroepithelial cells of its walls, the neurons and glia of the nervous system. The most anterior (front, or cranial) part of the neural plate, the prosencephalon, which is evident before neurulation begins, gives rise to the cerebral hemispheres and later cortex.
Cortical neuron development.
Cortical neurons are generated within the ventricular zone, next to the ventricles. At first, this zone contains neural stem cells, that transition to radial glial cells–progenitor cells, which divide to produce glial cells and neurons.
Radial glia.
The cerebral cortex is composed of a heterogenous population of cells that give rise to different cell types. The majority of these cells are derived from radial glia migration that form the different cell types of the neocortex and it is a period associated with an increase in neurogenesis. Similarly, the process of neurogenesis regulates lamination to form the different layers of the cortex. During this process there is an increase in the restriction of cell fate that begins with earlier progenitors giving rise to any cell type in the cortex and later progenitors giving rise only to neurons of superficial layers. This differential cell fate creates an inside-out topography in the cortex with younger neurons in superficial layers and older neurons in deeper layers. In addition, laminar neurons are stopped in S or G2 phase in order to give a fine distinction between the different cortical layers. Laminar differentiation is not fully complete until after birth since during development laminar neurons are still sensitive to extrinsic signals and environmental cues.
Although the majority of the cells that compose the cortex are derived locally from radial glia there is a subset population of neurons that migrate from other regions. Radial glia give rise to neurons that are pyramidal in shape and use glutamate as a neurotransmitter, however these migrating cells contribute neurons that are stellate-shaped and use GABA as their main neurotransmitter. These GABAergic neurons are generated by progenitor cells in the medial ganglionic eminence (MGE) that migrate tangentially to the cortex via the subventricular zone. This migration of GABAergic neurons is particularly important since GABA receptors are excitatory during development. This excitation is primarily driven by the flux of chloride ions through the GABA receptor, however in adults chloride concentrations shift causing an inward flux of chloride that hyperpolarizes postsynaptic neurons.
The glial fibers produced in the first divisions of the progenitor cells are radially oriented, spanning the thickness of the cortex from the ventricular zone to the outer, pial surface, and provide scaffolding for the migration of neurons outwards from the ventricular zone.
At birth there are very few dendrites present on the cortical neuron's cell body, and the axon is undeveloped. During the first year of life the dendrites become dramatically increased in number, such that they can accommodate up to a hundred thousand synaptic connections with other neurons. The axon can develop to extend a long way from the cell body.
Asymmetric division.
The first divisions of the progenitor cells are symmetric, which duplicates the total number of progenitor cells at each mitotic cycle. Then, some progenitor cells begin to divide asymmetrically, producing one postmitotic cell that migrates along the radial glial fibers, leaving the ventricular zone, and one progenitor cell, which continues to divide until the end of development, when it differentiates into a glial cell or an ependymal cell. As the G1 phase of mitosis is elongated, in what is seen as selective cell-cycle lengthening, the newly-born neurons migrate to more superficial layers of the cortex. The migrating daughter cells become the pyramidal cells of the cerebral cortex. The development process is time ordered and regulated by hundreds of genes and epigenetic regulatory mechanisms.
Layer organisation.
The layered structure of the mature cerebral cortex is formed during development. The first pyramidal neurons generated migrate out of the ventricular zone and subventricular zone, together with reelin-producing Cajal–Retzius neurons, from the preplate. Next, a cohort of neurons migrating into the middle of the preplate divides this transient layer into the superficial marginal zone, which will become layer I of the mature neocortex, and the subplate, forming a middle layer called the cortical plate. These cells will form the deep layers of the mature cortex, layers five and six. Later born neurons migrate radially into the cortical plate past the deep layer neurons, and become the upper layers (two to four). Thus, the layers of the cortex are created in an inside-out order. The only exception to this inside-out sequence of neurogenesis occurs in the layer I of primates, in which, in contrast to rodents, neurogenesis continues throughout the entire period of corticogenesis.
Cortical patterning.
The map of functional cortical areas, which include primary motor and visual cortex, originates from a 'protomap', which is regulated by molecular signals such as fibroblast growth factor FGF8 early in embryonic development. These signals regulate the size, shape, and position of cortical areas on the surface of the cortical primordium, in part by regulating gradients of transcription factor expression, through a process called cortical patterning. Examples of such transcription factors include the genes EMX2 and PAX6. Together, both transcription factors form an opposing gradient of expression. Pax6 is highly expressed at the rostral lateral pole, while Emx2 is highly expressed in the caudomedial pole. The establishment of this gradient is important for proper development. For example, mutations in Pax6 can cause expression levels of Emx2 to expand out of its normal expression domain, which would ultimately lead to an expansion of the areas normally derived from the caudal medial cortex, such as the visual cortex. On the contrary, if mutations in Emx2 occur, it can cause the Pax6-expressing domain to expand and result in the frontal and motor cortical regions enlarging. Therefore, researchers believe that similar gradients and signaling centers next to the cortex could contribute to the regional expression of these transcription factors.
Two very well studied patterning signals for the cortex include FGF and retinoic acid. If FGFs are misexpressed in different areas of the developing cortex, cortical patterning is disrupted. Specifically, when Fgf8 is increased in the anterior pole, Emx2 is downregulated and a caudal shift in the cortical region occurs. This ultimately causes an expansion of the rostral regions. Therefore, Fgf8 and other FGFs play a role in the regulation of expression of Emx2 and Pax6 and represent how the cerebral cortex can become specialized for different functions.
Rapid expansion of the cortical surface area is regulated by the amount of self-renewal of radial glial cells and is partly regulated by FGF and Notch genes. During the period of cortical neurogenesis and layer formation, many higher mammals begin the process of gyrification, which generates the characteristic folds of the cerebral cortex. Gyrification is regulated by a DNA-associated protein Trnp1 and by FGF and SHH signaling
Evolution.
Of all the different brain regions, the cerebral cortex shows the largest evolutionary variation and has evolved most recently. In contrast to the highly conserved circuitry of the medulla oblongata, for example, which serves critical functions such as regulation of heart and respiration rates, many areas of the cerebral cortex are not strictly necessary for survival. Thus, the evolution of the cerebral cortex has seen the advent and modification of new functional areas—particularly association areas that do not directly receive input from outside the cortex.
A key theory of cortical evolution is embodied in the radial unit hypothesis and related protomap hypothesis, first proposed by Rakic. This theory states that new cortical areas are formed by the addition of new radial units, which is accomplished at the stem cell level. The protomap hypothesis states that the cellular and molecular identity and characteristics of neurons in each cortical area are specified by cortical stem cells, known as radial glial cells, in a primordial map. This map is controlled by secreted signaling proteins and downstream transcription factors.
Function.
Connections.
The cerebral cortex is connected to various subcortical structures such as the thalamus and the basal ganglia, sending information to them along efferent connections and receiving information from them via afferent connections. Most sensory information is routed to the cerebral cortex via the thalamus. Olfactory information, however, passes through the olfactory bulb to the olfactory cortex (piriform cortex). The majority of connections are from one area of the cortex to another, rather than from subcortical areas; Braitenberg and Schüz (1998) claim that in primary sensory areas, at the cortical level where the input fibres terminate, up to 20% of the synapses are supplied by extracortical afferents but that in other areas and other layers the percentage is likely to be much lower.
Cortical areas.
The whole of the cerebral cortex was divided into 52 different areas in an early presentation by Korbinian Brodmann. These areas known as Brodmann areas, are based on their cytoarchitecture but also relate to various functions. An example is Brodmann area 17 which is the primary visual cortex.
In more general terms the cortex is typically described as comprising three parts: sensory, motor, and association areas.
Sensory areas.
The sensory areas are the cortical areas that receive and process information from the senses. Parts of the cortex that receive sensory inputs from the thalamus are called primary sensory areas. The senses of vision, hearing, and touch are served by the primary visual cortex, primary auditory cortex and primary somatosensory cortex respectively. In general, the two hemispheres receive information from the opposite (contralateral) side of the body. For example, the right primary somatosensory cortex receives information from the left limbs, and the right visual cortex receives information from the left visual field. The organization of sensory maps in the cortex reflects that of the corresponding sensing organ, in what is known as a topographic map. Neighboring points in the primary visual cortex, for example, correspond to neighboring points in the retina. This topographic map is called a retinotopic map. In the same way, there exists a tonotopic map in the primary auditory cortex and a somatotopic map in the primary sensory cortex. This last topographic map of the body onto the posterior central gyrus has been illustrated as a deformed human representation, the somatosensory homunculus, where the size of different body parts reflects the relative density of their innervation. Areas with much sensory innervation, such as the fingertips and the lips, require more cortical area to process finer sensation.
Motor areas.
The motor areas are located in both hemispheres of the cortex. The motor areas are very closely related to the control of voluntary movements, especially fine fragmented movements performed by the hand. The right half of the motor area controls the left side of the body, and vice versa.
Two areas of the cortex are commonly referred to as motor:
In addition, motor functions have been described for:
Just underneath the cerebral cortex are interconnected subcortical masses of grey matter called basal ganglia (or nuclei). The basal ganglia receive input from the substantia nigra of the midbrain and motor areas of the cerebral cortex, and send signals back to both of these locations. They are involved in motor control. They are found lateral to the thalamus. The main components of the basal ganglia are the caudate nucleus, the putamen, the globus pallidus, the substantia nigra, the nucleus accumbens, and the subthalamic nucleus. The putamen and globus pallidus are also collectively known as the lentiform nucleus, because together they form a lens-shaped body. The putamen and caudate nucleus are also collectively called the corpus striatum after their striped appearance.
Association areas.
The association areas are the parts of the cerebral cortex that do not belong to the primary regions. They function to produce a meaningful perceptual experience of the world, enable us to interact effectively, and support abstract thinking and language. The parietal, temporal, and occipital lobes – all located in the posterior part of the cortex – integrate sensory information and information stored in memory. The frontal lobe or prefrontal association complex is involved in planning actions and movement, as well as abstract thought. Globally, the association areas are organized as distributed networks. Each network connects areas distributed across widely spaced regions of the cortex. Distinct networks are positioned adjacent to one another yielding a complex series of interwoven networks. The specific organization of the association networks is debated with evidence for interactions, hierarchical relationships, and competition between networks.
In humans, association networks are particularly important to language function. In the past it was theorized that language abilities are localized in Broca's area in areas of the left inferior frontal gyrus, BA44 and BA45, for language expression and in Wernicke's area BA22, for language reception. However, the processes of language expression and reception have been shown to occur in areas other than just those structures around the lateral sulcus, including the frontal lobe, basal ganglia, cerebellum, and pons.
Clinical significance.
Neurodegenerative diseases such as Alzheimer's disease and Lafora disease, show as a marker, an atrophy of the grey matter of the cerebral cortex.
Other diseases of the central nervous system include neurological disorders such as epilepsy, movement disorders, and difficulties in speech (aphasia).
Brain damage from disease or trauma, can involve damage to a specific lobe such as in frontal lobe disorder, and associated functions will be affected. The blood-brain barrier that serves to protect the brain from infection can become compromised allowing entry to pathogens.
The developing fetus is susceptible to a range of environmental factors that can cause birth defects and problems in later development. Maternal alcohol consumption for example can cause fetal alcohol spectrum disorder. Other factors that can cause neurodevelopment disorders are toxicants such as drugs, and exposure to radiation as from X-rays. Infections can also affect the development of the cortex. A viral infection is one of the causes of lissencephaly, which results in a smooth cortex without gyrification.
A type of electrocorticography called cortical stimulation mapping is an invasive procedure that involves placing electrodes directly onto the exposed brain in order to localise the functions of specific areas of the cortex. It is used in clinical and therapeutic applications including pre-surgical mapping.
Genes associated with cortical disorders.
There are a number of genetic mutations that can cause a wide range of genetic disorders of the cerebral cortex, including microcephaly, schizencephaly and types of lissencephaly. Chromosome abnormalities can also result causing a number of neurodevelopmental disorders such as fragile X syndrome and Rett syndrome.
MCPH1 codes for microcephalin, and disorders in this and in ASPM are associated with microcephaly. Mutations in the gene NBS1 that codes for nibrin can cause Nijmegen breakage syndrome, characterised by microcephaly.
Mutations in EMX2, and COL4A1 are associated with schizencephaly, a condition marked by the absence of large parts of the cerebral hemispheres.
History.
In 1909, Korbinian Brodmann distinguished different areas of the neocortex based on cytoarchitectural difference and divided the cerebral cortex into 52 regions.
Rafael Lorente de Nó, a student of Santiago Ramon y Cajal identified more than 40 different types of cortical neurons based on the distribution of their dendrites and axons.
Other animals.
The cerebral cortex is derived from the pallium, a layered structure found in the forebrain of all vertebrates. The basic form of the pallium is a cylindrical layer enclosing fluid-filled ventricles. Around the circumference of the cylinder are four zones, the dorsal pallium, medial pallium, ventral pallium, and lateral pallium, which are thought respectively to give rise to the neocortex, hippocampus, amygdala, and olfactory cortex.
Until recently no counterpart to the cerebral cortex had been recognized in invertebrates. However, a study published in the journal "Cell" in 2010, based on gene expression profiles, reported strong affinities between the cerebral cortex and the mushroom bodies of the ragworm "Platynereis dumerilii". Mushroom bodies are structures in the brains of many types of worms and arthropods that are known to play important roles in learning and memory; the genetic evidence indicates a common evolutionary origin, and therefore indicates that the origins of the earliest precursors of the cerebral cortex date back to the early Precambrian era.