Thrombus

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Thrombus

 

Thrombus
Other names	Blood clot
Diagram of a thrombus (blood clot) that has blocked a blood vessel valve
Specialty	Vascular surgery

A thrombus, colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to prevent bleeding, but can be harmful in thrombosis, when clots obstruct blood flow through healthy blood vessels.

Mural thrombi are thrombi that adhere to the wall of a blood vessel. They occur in large vessels such as the heart and aorta, and can restrict blood flow but usually do not block it entirely. They appear grey-red with alternating light and dark lines (known as lines of Zahn) which represent bands of entrapped white blood cells and red blood cells (darker).

Cause

Virchow's triad describes the pathogenesis of thrombus formation:

1. Endothelial injury: Injury to the endothelium (interior surface of blood vessel), causing platelet activation and aggregation
   • Common causes include: trauma, smoking, hypertension, atheroma
2. Stasis: Blood stasis promotes greater contact between platelets/coagulative factors with vascular endothelium.
   • Common causes of stasis include anything that leads to prolonged immobility and reduced blood flow such as: trauma/broken bones and extended air travel
3. Hypercoagulability (also called thrombophilia; any disorder of the blood that predisposes to thrombosis)
   • Common causes include: cancer (leukaemia), Factor V mutation (Leiden) - prevents Factor V inactivation leading to increased coagulability.

Disseminated intravascular coagulation (DIC) involves widespread microthrombi formation throughout the majority of the blood vessels. This is due to excessive consumption of coagulation factors and subsequent activation of fibrinolysis using all of the body's available platelets and clotting factors. The end result is hemorrhaging and ischaemic necrosis of tissue/organs. Causes are septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas. DIC may also be seen in pregnant females. Treatment involves the use of fresh frozen plasma to restore the level of clotting factors in the blood, as well as platelets and heparin to prevent further thrombi formation. 

Classification

Thrombi are classified in three major groups depending on the relative amount of platelets and red blood cells (RBCs). The three major groups are:

1. White thrombi (characterized by predominance of platelets)
2. Red thrombi (characterized by predominance of red blood cells)
3. Mixed thrombi (with features of both white and red thrombi - an intermediate).

Pathophysiology

Animation of the formation of an occlusive thrombus in a vein. A few platelets attach themselves to the valve lips, constricting the opening and causing more platelets and red blood cells to aggregate and coagulate. Coagulation of unmoving blood on both sides of the blockage may propagate a clot in both directions.

A thrombus occurs when the hemostatic process, which normally occurs in response to injury, becomes activated in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut off (termed an occlusive thrombus), resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is considered an embolus.

Some of the conditions which increase the risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack (also known as a myocardial infarction), extended periods of inactivity, and genetic or disease-related deficiencies in the blood's clotting abilities.

Formation

Platelet activation occurs through injuries that damage the endothelium of the blood vessels, exposing the enzyme called factor VII, a protein normally circulating within the vessels, to the tissue factor, which is a protein encoded by the F3 gene. The platelet activation can potentially cause a cascade, eventually leading to the formation of the thrombus. This process is regulated through thromboregulation.

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  Illustration Comparing Normal Artery vs Diseased Artery with a Blood Clot
  
  
  
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  Micrograph showing a thrombus (center of image) within a blood vessel of the placenta. H&E stain.
  
  
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  Illustration depicting thrombus formation over arterial plaque.
  

Prevention and treatment

Blood clot prevention and treatment reduce the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are used to inhibit the formation and growth of existing thrombi, with the former used for acute anticoagulation while the latter is used for long-term anticoagulation. The mechanism of action of heparin and warfarin are different as they work on different pathways of the coagulation cascade. Heparin works by binding to and activating the enzyme inhibitor antithrombin III, an enzyme that acts by inactivating thrombin and factor Xa. In contrast, warfarin works by inhibiting vitamin K epoxide reductase, an enzyme needed to synthesize vitamin K dependent clotting factors II, VII, IX, and X. Bleeding time with heparin and warfarin therapy can be measured with the partial thromboplastin time (PTT) and prothrombin time (PT), respectively.

Some treatments have been derived from bacteria. One drug is streptokinase, which is an enzyme secreted by several streptococcal bacteria. This drug is administered intravenously and can be used to dissolve blood clots in coronary vessels. However, streptokinase is nonspecific and can digest almost any protein, which can lead to many secondary problems. Another clot-dissolving enzyme that works faster and is more specific is tissue plasminogen activator (tPA). This drug is made by transgenic bacteria and it converts plasminogen into the clot-dissolving enzyme, plasmin. There are also some anticoagulants that come from animals that work by dissolving fibrin. For example, Haementeria ghilianii, an Amazon leech, produces an enzyme called hementin from its salivary glands. As of 2012, this enzyme has been successfully produced by genetically engineered bacteria and is administered to cardiac patients. 

More recent research indicates that tPA could have toxic effects in the central nervous system. In cases of severe stroke, tPA can cross the blood-brain barrier and enter interstitial fluid, where it then increases excitotoxicity, potentially affecting permeability of the blood-brain barrier, and may even cause cerebral hemorrhaging.

Prognosis

Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization.

1. Propagation of a thrombus occurs towards the direction of the heart and involves the accumulation of additional platelets and fibrin. This means that it is anterograde in veins or retrograde in arteries.
2. Embolization occurs when the thrombus breaks free from the vascular wall and becomes mobile, thereby traveling to other sites in the vasculature. A venous embolus (mostly from deep vein thrombosis in the lower limbs) will travel through the systemic circulation, reach the right side of the heart, and travel through the pulmonary artery, resulting in a pulmonary embolism. Arterial thrombosis resulting from hypertension or atherosclerosis can become mobile and the resulting emboli can occlude any artery or arteriole downstream of the thrombus formation. This means that cerebral stroke, myocardial infarction, or any other organ can be affected.
3. Dissolution occurs when the fibrinolytic mechanisms break up the thrombus and blood flow is restored to the vessel. This may be aided by fibrinolytic drugs such as Tissue Plasminogen Activator (tPA) in instances of coronary artery occlusion. The best response to fibrinolytic drugs is within a couple of hours, before the fibrin meshwork of the thrombus has been fully developed.
4. Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. If recanalization proceeds it provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus but may not restore sufficient blood flow for the metabolic needs of the downstream tissue.

Embolism

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Embolism

 

Embolism
Micrograph of embolic material in the artery of a kidney. The kidney was surgically removed because of cancer. H&E stain.
Specialty	Vascular surgery

An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), or foreign material. An embolism can cause partial or total blockage of blood flow in the affected vessel. Such a blockage (a vascular occlusion) may affect a part of the body distant from the origin of the embolus. An embolism in which the embolus is a piece of thrombus is called a thromboembolism.

An embolism is usually a pathological event, i.e., accompanying illness or injury. Sometimes it is created intentionally for a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Such therapy is called embolization.

Classification

There are different types of embolism, some of which are listed below.

Embolism can be classified based on where it enters the circulation, either in arteries or in veins. Arterial embolism are those that follow and, if not dissolved on the way, lodge in a more distal part of the systemic circulation. Sometimes, multiple classifications apply; for instance a pulmonary embolism is classified as an arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins, e.g. deep vein thrombosis. 

Arterial

Arterial embolism can cause occlusion in any part of the body. It is a major cause of infarction (tissue death from blockage of the blood supply).

An embolus lodging in the brain from either the heart or a carotid artery will most likely be the cause of a stroke due to ischemia.

An arterial embolus might originate in the heart (from a thrombus in the left atrium, following atrial fibrillation or be a septic embolus resulting from endocarditis). Emboli of cardiac origin are frequently encountered in clinical practice. Thrombus formation within the atrium occurs mainly in patients with mitral valve disease, and especially in those with mitral valve stenosis (narrowing), with atrial fibrillation (AF). In the absence of AF, pure mitral regurgitation has a low incidence of thromboembolism.

The risk of emboli forming in AF depends on other risk factors such as age, hypertension, diabetes, recent heart failure, or previous stroke. Thrombus formation can also take place within the ventricles, and it occurs in approximately 30% of anterior-wall myocardial infarctions, compared with only 5% of inferior ones. Some other risk factors are poor ejection fraction (<35 a="" af.="" after="" and="" first="" href="https://en.wikipedia.org/wiki/Aneurysm" in="" infarct="" infarction="" left-ventricle="" months="" of="" presence="" size="" the="" three="" title="Aneurysm">aneurysms

have a 10% risk of emboli forming.

Patients with prosthetic valves also carry a significant increase in risk of thromboembolism. Risk varies, based on the valve type (bioprosthetic or mechanical); the position (mitral or aortic); and the presence of other factors such as AF, left-ventricular dysfunction, and previous emboli.

Emboli often have more serious consequences when they occur in the so-called "end circulation": areas of the body that have no redundant blood supply, such as the brain and heart. 

Venous

Assuming a normal circulation, an embolus formed in a systemic vein will always impact in the lungs, after passing through the right side of the heart. This will form a pulmonary embolism that will result in a blockage of the main artery of the lung and can be a complication of deep-vein thrombosis. The most common sites of origin of pulmonary emboli are the femoral veins. The deep veins of the calf are the most common sites of actual thrombi. 

Paradoxical (venous to arterial)

In paradoxical embolism, also known as crossed embolism, an embolus from the veins crosses to the arterial blood system. This is generally found only with heart problems such as septal defects (holes in the cardiac septum) between the atria or ventricles. The most common such abnormality is patent foramen ovale, occurring in about 25% of the adult population, but here the defect functions as a valve which is normally closed, because pressure is slightly higher in the left side of the heart. Sometimes, for example if a patient coughs just when an embolus is passing, it might cross to the arterial system. 

Direction

The direction of the embolus can be one of two types:

• Anterograde
• Retrograde

In anterograde embolism, the movement of emboli is in the direction of blood flow. In retrograde embolism, the emboli move in opposition to the blood flow direction; this is usually significant only in blood vessels with low pressure (veins) or with emboli of high weight. 

Etymology

The word embolism comes from the Greek ἐμβολισμός, meaning "interposition".

Vascular dementia

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Vascular_dementia

 

Vascular dementia
Other names	Arteriosclerotic dementia (in the ICD-9) Multi-infarct dementia (in the ICD-10) Vascular cognitive impairment
Specialty	Psychiatry, neurology

Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive decline that occurs step by step. The term refers to a syndrome consisting of a complex interaction of cerebrovascular disease and risk factors that lead to changes in the brain structures due to strokes and lesions, and resulting changes in cognition. The temporal relationship between a stroke and cognitive deficits is needed to make the diagnosis.

Signs and symptoms

Differentiating dementia syndromes can be challenging, due to the frequently overlapping clinical features and related underlying pathology. In particular, Alzheimer's dementia often co-occurs with vascular dementia.

People with vascular dementia present with progressive cognitive impairment, acutely or subacutely as in mild cognitive impairment, frequently step-wise, after multiple cerebrovascular events (strokes). Some people may appear to improve between events and decline after further silent strokes. A rapidly deteriorating condition may lead to death from a stroke, heart disease, or infection.

Signs and symptoms are cognitive, motor, behavioral, and for a significant proportion of patients also affective. These changes typically occur over a period of 5–10 years. Signs are typically the same as in other dementias, but mainly include cognitive decline and memory impairment of sufficient severity as to interfere with activities of daily living, sometimes with presence of focal neurologic signs, and evidence of features consistent with cerebrovascular disease on brain imaging (CT or MRI). The neurologic signs localizing to certain areas of the brain that can be observed are hemiparesis, bradykinesia, hyperreflexia, extensor plantar reflexes, ataxia, pseudobulbar palsy, as well as gait problems and swallowing difficulties. People have patchy deficits in terms of cognitive testing. They tend to have better free recall and fewer recall intrusions when compared with patients with Alzheimer's disease. In the more severely affected patients, or patients affected by infarcts in Wernicke's or Broca's areas, specific problems with speaking called dysarthrias and aphasias may be present.

In small vessel disease, the frontal lobes are often affected. Consequently, patients with vascular dementia tend to perform worse than their Alzheimer's disease counterparts in frontal lobe tasks, such as verbal fluency, and may present with frontal lobe problems: apathy, abulia (lack of will or initiative), problems with attention, orientation, and urinary incontinence. They tend to exhibit more perseverative behavior. VaD patients may also present with general slowing of processing ability, difficulty shifting sets, and impairment in abstract thinking. Apathy early in the disease is more suggestive of vascular dementia.

Rare genetic disorders that cause vascular lesions in the brain have other presentation patterns. As a rule, they tend to occur earlier in life and have a more aggressive course. In addition, infectious disorders, such as syphilis, can cause arterial damage, strokes, and bacterial inflammation of the brain. 

Causes

Vascular dementia can be caused by ischemic or hemorrhagic infarcts affecting multiple brain areas, including the anterior cerebral artery territory, the parietal lobes, or the cingulate gyrus. On rare occasion, infarcts in the hippocampus or thalamus are the cause of dementia. A history of stroke increases the risk of developing dementia by around 70%, and recent stroke increases the risk by around 120%. Brain vascular lesions can also be the result of diffuse cerebrovascular disease, such as small vessel disease.

Risk factors for vascular dementia include age, hypertension, smoking, hypercholesterolemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease. Other risk factors include geographic origin, genetic predisposition, and prior strokes.

Vascular dementia can sometimes be triggered by cerebral amyloid angiopathy, which involves accumulation of beta amyloid plaques in the walls of the cerebral arteries, leading to breakdown and rupture of the vessels. Since amyloid plaques are a characteristic feature of Alzheimer's disease, vascular dementia may occur as a consequence. Cerebral amyloid angiopathy can, however, appear in people with no prior dementia condition. Amyloid beta accumulation is often present in cognitively normal elderly people.

Two reviews of 2018 and 2019 found potentially an association between celiac disease and vascular dementia.

Diagnosis

Several specific diagnostic criteria can be used to diagnose vascular dementia, including the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, the International Classification of Diseases, Tenth Edition (ICD-10) criteria, the National Institute of Neurological Disorders and Stroke criteria, Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, the Alzheimer's Disease Diagnostic and Treatment Center criteria, and the Hachinski Ischemic Score (after Vladimir Hachinski).

The recommended investigations for cognitive impairment include: blood tests (for anemia, vitamin deficiency, thyrotoxicosis, infection, etc.), chest X-Ray, ECG, and neuroimaging, preferably a scan with a functional or metabolic sensitivity beyond a simple CT or MRI. When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging may be used to confirm a diagnosis of multi-infarct dementia in conjunction with evaluations involving mental status examination. In a person already having dementia, SPECT appears to be superior in differentiating multi-infarct dementia from Alzheimer's disease, compared to the usual mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.

The screening blood tests typically include full blood count, liver function tests, thyroid function tests, lipid profile, erythrocyte sedimentation rate, C reactive protein, syphilis serology, calcium serum level, fasting glucose, urea, electrolytes, vitamin B-12, and folate. In selected patients, HIV serology and certain autoantibody testing may be done.

Mixed dementia is diagnosed when people have evidence of Alzheimer's disease and cerebrovascular disease, either clinically or based on neuro-imaging evidence of ischemic lesions.

Pathology

Gross examination of the brain may reveal noticeable lesions and damage to blood vessels. Accumulation of various substances such as lipid deposits and clotted blood appear on microscopic views. The white matter is most affected, with noticeable atrophy (tissue loss), in addition to calcification of the arteries. Microinfarcts may also be present in the gray matter (cerebral cortex), sometimes in large numbers. Although atheroma of the major cerebral arteries is typical in vascular dementia, smaller vessels and arterioles are mainly affected.

Prevention

Early detection and accurate diagnosis are important, as vascular dementia is at least partially preventable. Ischemic changes in the brain are irreversible, but the patient with vascular dementia can demonstrate periods of stability or even mild improvement. Since stroke is an essential part of vascular dementia, the goal is to prevent new strokes. This is attempted through reduction of stroke risk factors, such as high blood pressure, high blood lipid levels, atrial fibrillation, or diabetes mellitus. Meta-analyses have found that medications for high blood pressure are effective at prevention of pre-stroke dementia, which means that high blood pressure treatment should be started early. These medications include angiotensin converting enzyme inhibitors, diuretics, calcium channel blockers, sympathetic nerve inhibitors, angiotensin II receptor antagonists or adrenergic antagonists. Elevated lipid levels, including HDL, were found to increase risk of vascular dementia. However, six large recent reviews showed that therapy with statin drugs was ineffective in treatment or prevention of this dementia. Aspirin is a medication that is commonly prescribed for prevention of strokes and heart attacks; it is also frequently given to patients with dementia. However, its efficacy in slowing progression of dementia or improving cognition has not been supported by studies. Smoking cessation and Mediterranean diet have not been found to help patients with cognitive impairment; physical activity was consistently the most effective method of preventing cognitive decline.

Treatment

Currently, there are no medications that have been approved specifically for prevention or treatment of vascular dementia. The use of medications for treatment of Alzheimer's dementia, such as cholinesterase inhibitors and memantine, has shown small improvement of cognition in vascular dementia. This is most likely due to the drugs' actions on co-existing AD-related pathology. Multiple studies found a small benefit in VaD treatment with: memantine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; cholinesterase inhibitors galantamine, donepezil, rivastigmine; and ginkgo biloba extract.

In those with celiac disease or non-celiac gluten sensitivity, a strict gluten-free diet may relieve symptoms of mild cognitive impairment. It should be started as soon as possible. There is no evidence that a gluten free diet is useful against advanced dementia. People with no digestive symptoms are less likely to receive early diagnosis and treatment.

General management of dementia includes referral to community services, aid with judgment and decision-making regarding legal and ethical issues (e.g., driving, capacity, advance directives), and consideration of caregiver stress. Behavioral and affective symptoms deserve special consideration in this patient group. These problems tend to resist conventional psychopharmacological treatment, and often lead to hospital admission and placement in permanent care. 

Prognosis

Many studies have been conducted to determine average survival of patients with dementia. The studies were frequently small and limited, which caused contradictory results in the connection of mortality to the type of dementia and the patient's gender. A very large study conducted in Netherlands in 2015 found that the one-year mortality was three to four times higher in patients after their first referral to a day clinic for dementia, when compared to the general population. If the patient was hospitalized for dementia, the mortality was even higher than in patients hospitalized for cardiovascular disease. Vascular dementia was found to have either comparable or worse survival rates when compared to Alzheimer's Disease; another very large 2014 Swedish study found that the prognosis for VaD patients was worse for male and older patients.

Unlike Alzheimer's Disease, which weakens the patient, causing them to succumb to bacterial infections like pneumonia, vascular dementia can be a direct cause of death due to the possibility of a fatal interruption in the brain's blood supply. 

Epidemiology

Vascular dementia is the second-most-common form of dementia after Alzheimer's disease (AD) in older adults. The prevalence of the illness is 1.5% in Western countries and approximately 2.2% in Japan. It accounts for 50% of all dementias in Japan, 20% to 40% in Europe and 15% in Latin America. 25% of stroke patients develop new-onset dementia within one year of their stroke. One study found that in the United States, the prevalence of vascular dementia in all people over the age of 71 is 2.43%, and another found that the prevalence of the dementias doubles with every 5.1 years of age. The incidence peaks between the fourth and the seventh decades of life and 80% of patients have a history of hypertension. 

A recent meta-analysis identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49–1.92; P < .00001; I² = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90–2.50; P < .00001; I² = 88%). Study characteristics did not modify these associations, with the exception of sex, which explained 50.2% of between-study heterogeneity for prevalent stroke. These results confirm that stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.

White matter

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/White_matter

 

White matter
Micrograph showing white matter with its characteristic fine meshwork-like appearance (left of image - lighter shade of pink) and grey matter, with the characteristic neuronal cell bodies (right of image - dark shade of pink). HPS stain.
Human brain right dissected lateral view, showing grey matter (the darker outer parts), and white matter (the inner and prominently whiter parts).
Details
Location	Central nervous system
Identifiers
Latin	substantia alba
MeSH	D066127
TA	A14.1.00.009
FMA	83929

White matter structure of human brain (taken by MRI).

White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution of action potentials, acting as a relay and coordinating communication between different brain regions.

White matter is named for its relatively light appearance resulting from the lipid content of myelin. However, the tissue of the freshly cut brain appears pinkish-white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color in prepared specimens is due to its usual preservation in formaldehyde. 

Structure

White matter

White matter is composed of bundles, which connect various gray matter areas (the locations of nerve cell bodies) of the brain to each other, and carry nerve impulses between neurons. Myelin acts as an insulator, which allows electrical signals to jump, rather than coursing through the axon, increasing the speed of transmission of all nerve signals.

The total number of long range fibers within a cerebral hemisphere is 2% of the total number of cortico-cortical fibers (across cortical areas) and is roughly the same number as those that communicate between the two hemispheres in the brain's largest white tissue structure, the corpus callosum. Schüz and Braitenberg note "As a rough rule, the number of fibres of a certain range of lengths is inversely proportional to their length."

White matter in nonelderly adults is 1.7–3.6% blood.

Grey matter

The other main component of the brain is grey matter (actually pinkish tan due to blood capillaries), which is composed of neurons. The substantia nigra is a third colored component found in the brain that appears darker due to higher levels of melanin in dopaminergic neurons than its nearby areas. Note that white matter can sometimes appear darker than grey matter on a microscope slide because of the type of stain used. Cerebral- and spinal white matter do not contain dendrites, neural cell bodies, or shorter axons, which can only be found in grey matter. 

Location

White matter forms the bulk of the deep parts of the brain and the superficial parts of the spinal cord. Aggregates of grey matter such as the basal ganglia (caudate nucleus, putamen, globus pallidus, substantia nigra, subthalamic nucleus, nucleus accumbens) and brainstem nuclei (red nucleus, cranial nerve nuclei) are spread within the cerebral white matter.

The cerebellum is structured in a similar manner as the cerebrum, with a superficial mantle of cerebellar cortex, deep cerebellar white matter (called the "arbor vitae") and aggregates of grey matter surrounded by deep cerebellar white matter (dentate nucleus, globose nucleus, emboliform nucleus, and fastigial nucleus). The fluid-filled cerebral ventricles (lateral ventricles, third ventricle, cerebral aqueduct, fourth ventricle) are also located deep within the cerebral white matter.

Myelinated axon length

Men have more white matter than women both in volume and in length of myelinated axons. At the age of 20, the total length of myelinated fibers in men is 176,000 km while that of a woman is 149,000 km. There is a decline in total length with age of about 10% each decade such that a man at 80 years of age has 97,200 km and a female 82,000 km. Most of this reduction is due to the loss of thinner fibers.

Function

White matter is the tissue through which messages pass between different areas of gray matter within the central nervous system. The white matter is white because of the fatty substance (myelin) that surrounds the nerve fibers (axons). This myelin is found in almost all long nerve fibers, and acts as an electrical insulation. This is important because it allows the messages to pass quickly from place to place. 

Unlike gray matter, which peaks in development in a person's twenties, the white matter continues to develop, and peaks in middle age.

Research

Multiple sclerosis (MS) is the most common of the inflammatory demyelinating diseases of the central nervous system which affect white matter. In MS lesions, the myelin sheath around the axons is deteriorated by inflammation. Alcohol use disorders are associated with a decrease in white matter volume.

Amyloid plaques in white matter may be associated with Alzheimer's disease and other neurodegenerative diseases. Other changes that commonly occur with age include the development of leukoaraiosis, which is a rarefaction of the white matter that can be correlated with a variety of conditions, including loss of myelin pallor, axonal loss, and diminished restrictive function of the blood–brain barrier.

White matter lesions on magnetic resonance imaging are linked to several adverse outcomes, such as cognitive impairment and depression. White matter hyperintensity are more than often present with vascular dementia, particularly among small vessel/subcortical subtypes of vascular dementia.

Volume

Smaller volumes (in terms of group averages) of white matter might be associated with larger deficits in attention, declarative memory, executive functions, intelligence, and academic achievement. However, volume change is continuous throughout one's lifetime due to neuroplasticity, and is a contributing factor rather than determinant factor of certain functional deficits due to compensating effects in other brain regions. The integrity of white matter declines due to aging. Nonetheless, regular aerobic exercise appears to either postpone the aging effect or in turn enhance the white matter integrity in the long run. Changes in white matter volume due to inflammation or injury may be a factor in the severity of obstructive sleep apnea.

Imaging

The study of white matter has been advanced with the neuroimaging technique called diffusion tensor imaging where magnetic resonance imaging (MRI) brain scanners are used. As of 2007, more than 700 publications have been published on the subject.

A 2009 paper by Jan Scholz and colleagues used diffusion tensor imaging (DTI) to demonstrate changes in white matter volume as a result of learning a new motor task (e.g. juggling). The study is important as the first paper to correlate motor learning with white matter changes. Previously, many researchers had considered this type of learning to be exclusively mediated by dendrites, which are not present in white matter. The authors suggest that electrical activity in axons may regulate myelination in axons. Or, gross changes in the diameter or packing density of the axon might cause the change. A more recent DTI study by Sampaio-Baptista and colleagues reported changes in white matter with motor learning along with increases in myelination.

Language center

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Language_center

The term language center (or more accurately centers, e.g. Broca's area and Wernicke's area) refers to the areas of the brain which serve a particular function for speech processing and production. Language is a core system, which gives humans the capacity to solve difficult problems and provides them with a unique type of social interaction. Language allows individuals to attribute symbols (e.g. words or signs) to specific concepts and display them through sentences and phrases that follow proper grammatical rules. Moreover, speech is the mechanism in which language is orally expressed.

Language Areas of the brain. The Angular Gyrus is represented in orange, Supramarginal Gyrus is represented in yellow, Broca's area is represented in blue, Wernicke's area is represented in green and the Primary Auditory Cortex is represented in pink.

Information is exchanged in a larger system including language-related regions. These regions are connected by white matter fiber tracts that make possible the transmission of information between regions. The white matter fibers bunches were recognized to be important for language production after suggesting that it is possible to make a connection between multiple language centers. The three classical language areas that are involved in language production and processing are Broca’s and Wernicke’s areas, and angular gyrus.

Broca’s area

Broca's Area was first suggested to play a role in speech function by the French neurologist and anthropologist Paul Broca in 1861. The basis for this discovery was the analysis of speech problems resulting from injuries to this region of the brain, located in the inferior frontal gyrus. Paul Broca had a patient called Leborgne who could only pronounce the word “tan” when speaking. Paul Broca, after working with another patient with similar impairment, concluded that damage in the inferior frontal gyrus affected articulate language.

Broca’s area is well-known for being the syntactic processing  “center”. It has been known since Paul Broca associated speech production with an area in the posterior inferior frontal gyrus, which he called “Broca’s area”. Although this area is in charge of speech production, its particular role in the language system is unknown. However, it is involved in phonological, semantic, and syntactic processing and working memory. The anterior region of Broca’s area is involved in semantic processing, while the posterior region in the phonological processing (Bohsali, 2015). Moreover, the whole of Broca’s area has been shown to have a higher activation while doing reading tasks than other types of tasks.

In a simple explanation of speech production, this area approaches phonological word representation chronologically divided into segments of syllables which then is sent to different motor areas where they are converted into a phonetic code. The study of how this area produces speech has been made with paradigms using both single and complex words.

Broca’s area is correlated with phonological segmentation, unification, and syntactic processing, which are all connected to linguistic information. This area, although it synchronizes the transformation of information within cortical systems involved in spoken word production, does not contribute to the production of single words. The inferior frontal lobe is the one in charge of word production.

Broca's and Wernicke's area

 

Language Areas of the brain. The Angular Gyrus is represented in orange, Supramarginal Gyrus is represented in yellow, Broca's area is represented in blue, Wernicke's area is represented in green and the Primary Auditory Cortexis represented in pink.

 

Furthermore, Broca’s area is structurally related to the thalamus and both are engaged in language processing. The connectivity between both areas is two thalamic nuclei, the pulvinar, and the ventral nucleus, which are involved in language processing and linguistic functions similar to BA 44 and 45 in Broca’s area. Pulvinar is connected to many frontal regions of the frontal cortex and ventral nucleus is involved in speech production. The frontal speech regions of the brain have been shown to participate in speech sound perception.

Broca's Area is today still considered an important language center, playing a central role in processing syntax, grammar, and sentence structure. 

Wernicke’s area

Wernicke’s area was named for German doctor Carl Wernicke, who discovered it in 1874 in the course of his research into aphasias (loss of ability to speak).This area of the brain is involved in language comprehension. Therefore, Wernicke’s area is for understanding oral language. Besides Wernicke’s area, the left posterior superior temporal gyrus (pSTG), middle temporal gyrus (MTG), inferior temporal gyrus (ITG), supramarginal gyrus (SMG), and angular gyrus (AG) participate in language comprehension. Therefore, language comprehension is not located in a specific area. Contrarily, it involves large regions of the inferior parietal lobe and left temporal.

While the finale of speech production is a sequence of muscle movements, the activation of knowledge about the sequence of phonemes (consonants and vowel speech sounds) that creates a word is a phonological retrieval. Wernicke’s area contributes to phonological retrieval. All speech production tasks (e.g. word retrieval, repetition, and reading aloud) require phonological retrieval. The phonological retrieval system involved in speech repetition is the auditory phoneme perception system and the visual letter perception system is the one that serves for reading aloud. The communicative speech production entails a phase preceding phonological retrieval. The speech comprehension implicates representing sequences of phonemes onto word meaning.

Angular gyrus

The angular gyrus is an important element in processing concrete and abstract concepts. It also has a role in verbal working memory during retrieval for verbal information and in visual memory for when turning written language into spoken language. The left AG is activated in semantic processing requiring concept retrieval and conceptual integration. Moreover, the left AG is activated during problems of multiplication and addition requiring retrieval of arithmetic factors in verbal memory. Therefore, it is involved in verbal coding of numbers.

Insular cortex

The insula is implicated in speech and language, partaking of functional and structural connections with motor, linguistic, sensory, and limbic brain areas. The knowledge about the function of the insula in speech production comes from different studies with patients who suffered from apraxia of speech. These studies have led researchers to know about the involvement of different parts of the insula. These parts are: the left anterior insula, which is related to speech production; and the bilateral anterior insula, involved in misleading speech comprehension.

Speech and language disorders

Many different sources state that the study of the brain and therefore, language disorders, originated in the 19th century and linguistic analysis of those disorders began throughout the 20th century. Studying language impairments in the brain after injuries aids to comprehend how the brain works and how it changes after an injury. When this happens, the brain suffers an impairment that is referred to as “aphasia”. Lesions to Broca's Area resulted primarily in disruptions to speech production; damage to Wernicke's Area, which is located in the lower part of the temporal lobe, lead mainly to disruptions in speech reception.

There are numerous distinctive ways in which language can be affected. Phonemic paraphasia, an attribute of conduction aphasia and Wernicke aphasia, is not the speech comprehension impairment. Instead, it is the speech production damage, where the desire phonemes are selected erroneously or in an incorrect sequence. Therefore, although Wernicke’s aphasia, a combination of phonological retrieval and semantic systems impairment, affects speech comprehension, it also involves speech production damage. Phonemic paraphasia and anomia (impaired word retrieval) are the results of phonological retrieval impairment.

Another lesion that involves impairment in language production and processing is the “apraxia of speech”, a difficulty synchronizing articulators essential for speech production. This lesion is located in the superior pre-central gyrus of the insula and is more likely to occur to patients with Broca’s aphasia. Dominant ventral anterior (VA) nucleus, another type of lesion, is the result of word-finding and semantic paraphasia’s difficulties engaging in language processing. Moreover, individuals with thalamic lesions experience difficulties linking semantic concepts with correct phonological representations in word production.

Dyslexia is a language processing disorder. It involves learning difficulties such as reading, writing, word recognition, phonological recording, numeracy, and spelling. Although having access to appropriate intervention during childhood, these difficulties continue throughout the lifespan. Moreover, children are diagnosed with dyslexia when more than one factor affecting learning, such as reading, appears visible. Children diagnosed with dyslexia that have difficulties in concrete cognitive functioning is called an assumption of specificity, and it helps to diagnose dyslexia.

Some characteristics that distinguish dyslexics are incompetent phonological processing abilities causing misread of unfamiliar words and affecting comprehension; inadequacy of working memory affecting speaking, reading, and writing; errors in oral reading; oral skills difficulties as expressing oneself; and writing skills problems like expressing and spelling errors. Dyslexics not only experience learning difficulties but also other secondary characteristics as having difficulties organizing, planning, social interactions, motor skills, visual perception, and short-term memory. These characteristics affect personal and academic life.

Dysarthria is a motor speech disorder caused by damage in the central and/or peripheral nervous system and it is related to degenerative neurological diseases, such as Parkinson’s disease, cerebrovascular accident (CVA) and traumatic brain injury (TBI). Dysarthria is caused by a mechanical difficulty in the vocal cords or neurological disease-producing abnormal articulation of phonemes, such as instead of “b” a “p”. A type of dyspraxia based on distortions of words is called apraxic dysarthria This type is related to facial apraxia and motor aphasia if Broca’s area is involved.

Current scientific consensus

Improvements in computer technology, in the late 20th century, has allowed a better understanding of the correlation between brain and language, and the disorder that this entails. This improvement has permitted a better visualization of the brain structure in high resolution three-dimensional images. It has also allowed to observe brain activity through the blood flow (Dronkers, Ivanova, & Baldo, 2017).

New medical imaging techniques such as PET and fMRI have allowed researchers to generate pictures showing which areas of a living brain are active at a given time. Functional magnetic resonance imaging (fMRI) is a technique used for locating, in the brain, particular functions to different activity related. This technique shows the location and magnitude of neural activity variations, influenced by external stimulation and fluctuation at rest. MRI is a technique that was developed in the 20th century to observe brain activity in healthy and abnormal brains. Diffusion-weighted magnetic resonance imaging or diffusion tensor imaging (DTI) is a technique use for track white matter bundles in vivo and gives information of the internal fibrous structure by the measure of water diffusion. This diffusion tensor is used for infer white matter connectivity.

In the past, research was primarily based on observations of loss of ability resulting from damage to the cerebral cortex. Indeed, medical imaging has represented a radical step forward for research on speech processing. Since then, a whole series of relatively large areas of the brain are involved in speech processing. In more recent research, subcortical regions (those lying below the cerebral cortex such as the putamen and the caudate nucleus), as well as the pre-motor areas (BA 6), have received increased attention. It is now generally assumed that the following structures of the cerebral cortex near the primary and secondary auditory cortices play a fundamental role in speech processing:

• Superior temporal gyrus (STG): morphosyntactic processing (anterior section), integration of syntactic and semantic information (posterior section)
• Inferior frontal gyrus (IFG, Brodmann area (BA) 45/47): syntactic processing, working memory
• Inferior frontal gyrus (IFG, BA 44): syntactic processing, working memory
• Middle temporal gyrus (MTG): lexical semantic processing
• Angular gyrus (AG): semantic processes (posterior temporal cortex)

The left hemisphere is usually dominant in right-handed people, although bilateral activations are not uncommon in the area of syntactic processing. It is now accepted that the right hemisphere plays an important role in the processing of suprasegmental acoustic features like prosody; which is “the rhythmic and melodic variations in speech”. There are two types of prosodic information: emotional prosody (right hemisphere), which is the emotional that the speaker gives to the speech, and linguistic prosody (left hemisphere), the syntactic and thematic structure of the speech.

Most areas of speech processing develop in the second year of life in the dominant half (hemisphere) of the brain, which often (though not necessarily) corresponds to the opposite of the dominant hand. 98% of right-handed people are left-hemisphere dominant, and the majority of left-handed people are as well.

Computerized tomographic (CT) scans is another technique of the 1970s, which produce low spatial resolution but provides the location of the injury in vivo. Moreover, Voxel-based Lesion Symptom Mapping (VLSM) and Voxel-Based Morphometry (VBM) techniques contributed to the understanding that specific brain regions have different roles when supporting speech processing.^[2] VLSM has been used to observe complex language functions sustained by different regions. Furthermore, VBM is a helpful technique to analysis language impairments related to neurodegenerative disease.

Older models

The differentiation of speech production into only two large sections of the brain (i.e. Broca's and Wernicke's areas), that was accepted long before the advent of medical imaging techniques, is now considered outdated. Broca's Area was first suggested to play a role in speech function by the French neurologist and anthropologist Paul Broca in 1861. The basis for this discovery was the analysis of speech problems resulting from injuries to this region of the brain, located in the inferior frontal gyrus. Lesions to Broca's Area resulted primarily in disruptions to speech production. Damage to Wernicke's Area, which is located in the lower part of the temporal lobe, lead mainly to disruptions in speech reception. This area was named for German doctor Carl Wernicke, who discovered it in 1874 in the course of his research into aphasias (loss of ability to speak).

Broca's Area is today still considered an important language center, playing a central role in processing syntax, grammar, and sentence structure.

In summary, these early research efforts demonstrated that semantic and structural speech production takes place in different areas of the brain.