Speech repetition

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Speech_repetition

Children copy with their own mouths the words spoken by the mouths of those around them. That enables them to learn the pronunciation of words not already in their vocabulary.

Speech repetition occurs when individuals speak the sounds that they have heard another person pronounce or say. In other words, it is the saying by one individual of the spoken vocalizations made by another individual. Speech repetition requires the person repeating the utterance to have the ability to map the sounds that they hear from the other person's oral pronunciation to similar places and manners of articulation in their own vocal tract.

Such speech imitation often occurs independently of speech comprehension such as in speech shadowing in which people automatically say words heard in earphones, and the pathological condition of echolalia in which people reflexively repeat overheard words. That links to speech repetition of words being separate in the brain to speech perception. Speech repetition occurs in the dorsal speech processing stream, and speech perception occurs in the ventral speech processing stream. Repetitions are often incorporated unawares by that route into spontaneous novel sentences immediately or after delay after the storage in phonological memory.

In humans, the ability to map heard input vocalizations into motor output is highly developed because of the copying ability playing a critical role in children's rapid expansion of their spoken vocabulary. In older children and adults, that ability remains important, as it enables the continued learning of novel words and names and additional languages. That repetition is also necessary for the propagation of language from generation to generation. It has also been suggested that the phonetic units out of which speech is made have been selected upon by the process of vocabulary expansion and vocabulary transmissions because children prefer to copy words in terms of more easily imitated elementary units.

Properties

Automatic

Vocal imitation happens quickly: words can be repeated within 250-300 milliseconds both in normals (during speech shadowing) and during echolalia. The imitation of speech syllables possibly happens even more quickly: people begin imitating the second phone in the syllable [ao] earlier than they can identify it (out of the set [ao], [aæ] and [ai]). Indeed, "...simply executing a shift to [o] upon detection of a second vowel in [ao] takes very little longer than does interpreting and executing it as a shadowed response". Neurobiologically this suggests "...that the early phases of speech analysis yield information which is directly convertible to information required for speech production". Vocal repetition can be done immediately as in speech shadowing and echolalia. It can also be done after the pattern of pronunciation is stored in short-term memory or long-term memory. It automatically uses both auditory and where available visual information about how a word is produced.

The automatic nature of speech repetition was noted by Carl Wernicke, the late nineteenth century neurologist, who observed that "The primary speech movements, enacted before the development of consciousness, are reflexive and mimicking in nature..".

Independent of speech

Vocal imitation arises in development before speech comprehension and also babbling: 18-week-old infants spontaneously copy vocal expressions provided the accompanying voice matches. Imitation of vowels has been found as young as 12 weeks. It is independent of native language, language skills, word comprehension and a speaker's intelligence. Many autistic and some mentally disabled people engage in the echolalia of overheard words (often their only vocal interaction with others) without understanding what they echo. Reflex uncontrolled echoing of others words and sentences occurs in roughly half of those with Gilles de la Tourette syndrome. The ability to repeat words without comprehension also occurs in mixed transcortical aphasia where it links to the sparing of the short-term phonological store.

The ability to repeat and imitate speech sounds occurs separately to that of normal speech. Speech shadowing provides evidence of a 'privileged' input/output speech loop that is distinct to the other components of the speech system. Neurocognitive research likewise finds evidence of a direct (nonlexical) link between phonological analysis input and motor programming output.

Effector independent

Speech sounds can be imitatively mapped into vocal articulations in spite of vocal tract anatomy differences in size and shape due to gender, age and individual anatomical variability. Such variability is extensive making input output mapping of speech more complex than a simple mapping of vocal track movements. The shape of the mouth varies widely: dentists recognize three basic shapes of palate: trapezoid, ovoid, and triangular; six types of malocclusion between the two jaws; nine ways teeth relate to the dental arch and a wide range of maxillary and mandible deformities. Vocal sound can also vary due to dental injury and dental caries. Other factors that do not impede the sensory motor mapping needed for vocal imitation are gross oral deformations such as hare-lips, cleft palates or amputations of the tongue tip, pipe smoking, pencil biting and teeth clinching (such as in ventriloquism). Paranasal sinuses vary between individuals 20-fold in volume, and differ in the presence and the degree of their asymmetry.

Diverse linguistic vocalizations

Vocal imitation occurs potentially in regard to a diverse range of phonetic units and types of vocalization. The world's languages use consonantal phones that differ in thirteen imitable vocal tract place of articulations (from the lips to the glottis). These phones can potentially be pronounced with eleven types of imitable manner of articulations (nasal stops to lateral clicks). Speech can be copied in regard to its social accent, intonation, pitch and individuality (as with entertainment impersonators). Speech can be articulated in ways which diverge considerably in speed, timbre, pitch, loudness and emotion. Speech further exists in different forms such as song, verse, scream and whisper. Intelligible speech can be produced with pragmatic intonation and in regional dialects and foreign accents. These aspects are readily copied: people asked to repeat speech-like words imitate not only phones but also accurately other pronunciation aspects such as fundamental frequency, schwa-syllable expression, voice spectra and lip kinematics, voice onset times, and regional accent.

Language acquisition

Vocabulary expansion

In 1874 Carl Wernicke proposed that the ability to imitate speech plays a key role in language acquisition. This is now a widely researched issue in child development. A study of 17,000 one and two word utterances made by six children between 18 months to 25 months found that, depending upon the particular infant, between 5% and 45% of their words might be mimicked. These figures are minima since they concern only immediately heard words. Many words that may seem spontaneous are in fact delayed imitations heard days or weeks previously. At 13 months children who imitate new words (but not ones they already know) show a greater increase in noun vocabulary at four months and non noun vocabulary at eight months. A major predictor of vocabulary increase in both 20 months, 24 months, and older children between 4 and 8 years is their skill in repeating nonword phone sequences (a measure of mimicry and storage). This is also the case with children with Down's syndrome . The effect is larger than even age: in a study of 222 two-year-old children that had spoken vocabularies ranging between 3–601 words the ability to repeat nonwords accounted for 24% of the variance compared to 15% for age and 6% for gender (girls better than boys).

Nonvocabulary expansion uses of imitation

Imitation provides the basis for making longer sentences than children could otherwise spontaneously make on their own.^[35] Children analyze the linguistic rules, pronunciation patterns, and conversational pragmatics of speech by making monologues (often in crib talk) in which they repeat and manipulate in word play phrases and sentences previously overheard.^[36] Many proto-conversations involve children (and parents) repeating what each other has said in order to sustain social and linguistic interaction. It has been suggested that the conversion of speech sound into motor responses helps aid the vocal "alignment of interactions" by "coordinating the rhythm and melody of their speech".^[37] Repetition enables immigrant monolingual children to learn a second language by allowing them to take part in 'conversations'.^[38] Imitation related processes aids the storage of overheard words by putting them into speech based short- and long-term memory.^[39]

Language learning

The ability to repeat nonwords predicts the ability to learn second-language vocabulary.^[40] A study found that adult polyglots performed better in short-term memory tasks such as repeating nonword vocalizations compared to nonpolyglots though both are otherwise similar in general intelligence, visuo-spatial short-term memory and paired-associate learning ability.^[41] Language delay in contrast links to impairments in vocal imitation.^[42]

Speech repetition and phones

Electrical brain stimulation research upon the human brain finds that 81% of areas that show disruption of phone identification are also those in which the imitating of oral movements is disrupted and vice versa;^[43] Brain injuries in the speech areas show a 0.9 correlation between those causing impairments to the copying of oral movements and those impairing phone production and perception.^[44]

Mechanism

Spoken words are sequences of motor movements organized around vocal tract gesture motor targets.^[45] Vocalization due to this is copied in terms of the motor goals that organize it rather than the exact movements with which it is produced. These vocal motor goals are auditory. According to James Abbs^[46] 'For speech motor actions, the individual articulatory movements would not appear to be controlled with regard to three- dimensional spatial targets, but rather with regard to their contribution to complex vocal tract goals such as resonance properties (e.g., shape, degree of constriction) and or aerodynamically significant variables'. Speech sounds also have duplicable higher-order characteristics such as rates and shape of modulations and rates and shape of frequency shifts.^[47] Such complex auditory goals (which often link—though not always—to internal vocal gestures) are detectable from the speech sound which they create.

Neurology

Dorsal speech processing stream function

Two cortical processing streams exist: a ventral one which maps sound onto meaning, and a dorsal one, that maps sound onto motor representations. The dorsal stream projects from the posterior Sylvian fissure at the temporoparietal junction, onto frontal motor areas, and is not normally involved in speech perception.^[48] Carl Wernicke identified a pathway between the left posterior superior temporal sulcus (a cerebral cortex region sometimes called the Wernicke's area) as a centre of the sound "images" of speech and its syllables that connected through the arcuate fasciculus with part of the inferior frontal gyrus (sometimes called the Broca's area) responsible for their articulation.^[6] This pathway is now broadly identified as the dorsal speech pathway, one of the two pathways (together with the ventral pathway) that process speech.^[49] The posterior superior temporal gyrus is specialized for the transient representation of the phonetic sequences used for vocal repetition.^[50] Part of the auditory cortex also can represent aspects of speech such as its consonantal features.^[51]

Mirror neurons

Mirror neurons have been identified that both process the perception and production of motor movements. This is done not in terms of their exact motor performance but an inference of the intended motor goals with which it is organized.^[52] Mirror neurons that both perceive and produce the motor movements of speech have been identified.^[53] Speech is mirrored constantly into its articulations since speakers cannot know in advance that a word is unfamiliar and in need of repetition—which is only learnt after the opportunity to map it into articulations has gone. Thus, speakers if they are to incorporate unfamiliar words into their spoken vocabulary must by default map all spoken input.^[54]

Sign language

Words in sign languages, unlike those in spoken ones, are made not of sequential units but of spatial configurations of subword unit arrangements, the spatial analogue of the sonic-chronological morphemes of spoken language.^[55] These words, like spoken ones, are learnt by imitation. Indeed, rare cases of compulsive sign-language echolalia exist in otherwise language-deficient deaf autistic individuals born into signing families.^[55] At least some cortical areas neurobiologically active during both sign and vocal speech, such as the auditory cortex, are associated with the act of imitation.^[56]

Nonhuman animals

Birds

Birds learn their songs from those made by other birds. In several examples, birds show highly developed repetition abilities: the Sri Lankan Greater racket-tailed drongo (Dicrurus paradiseus) copies the calls of predators and the alarm signals of other birds^[57] Albert's lyrebird (Menura alberti) can accurately imitate the satin bowerbird (Ptilonorhynchus violaceus),^[58]

Research upon avian vocal motor neurons finds that they perceive their song as a series of articulatory gestures as in humans.^[59] Birds that can imitate humans, such as the Indian hill myna (Gracula religiosa), imitate human speech by mimicking the various speech formants, created by changing the shape of the human vocal tract, with different vibration frequencies of its internal tympaniform membrane.^[60] Indian hill mynahs also imitate such phonetic characteristics as voicing, fundamental frequencies, formant transitions, nasalization, and timing, through their vocal movements are made in a different way from those of the human vocal apparatus.^[60]

Nonhuman mammals

• Bottlenose dolphins can show spontaneous vocal mimicry of computer-generated whistles.^[61]
• Killer whales can mimic the barks of California sea lions.^[62]
• Harbor seals can mimic in a speech-like manner one or more English words and phrases^[63]
• Elephants can imitate trunk sounds.^[64]
• Lesser spear-nosed bat can learn their call structure from artificial playback.^[65]
• An orangutan has spontaneously copied the whistles of humans.^[66]

Apes

Apes taught language show an ability to imitate language signs with chimpanzees such as Washoe who was able to learn with his arms a vocabulary of 250 American Sign Language gestures. However, such human trained apes show no ability to imitate human speech vocalizations.

Introduction to genetics

From Wikipedia, the free encyclopedia

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

Genetics is the study of genes and tries to explain what they are and how they work. Genes are how living organisms inherit features or traits from their ancestors; for example, children usually look like their parents because they have inherited their parents' genes. Genetics tries to identify which traits are inherited and to explain how these traits are passed from generation to generation.

Some traits are part of an organism's physical appearance, such as eye color or height. Other sorts of traits are not easily seen and include blood types or resistance to diseases. Some traits are inherited through genes, which is the reason why tall and thin people tend to have tall and thin children. Other traits come from interactions between genes and the environment, so a child who inherited the tendency of being tall will still be short if poorly nourished. The way our genes and environment interact to produce a trait can be complicated. For example, the chances of somebody dying of cancer or heart disease seems to depend on both their genes and their lifestyle.

Genes are made from a long molecule called DNA, which is copied and inherited across generations. DNA is made of simple units that line up in a particular order within it, carrying genetic information. The language used by DNA is called genetic code, which lets organisms read the information in the genes. This information is the instructions for the construction and operation of a living organism.

The information within a particular gene is not always exactly the same between one organism and another, so different copies of a gene do not always give exactly the same instructions. Each unique form of a single gene is called an allele. As an example, one allele for the gene for hair color could instruct the body to produce much pigment, producing black hair, while a different allele of the same gene might give garbled instructions that fail to produce any pigment, giving white hair. Mutations are random changes in genes and can create new alleles. Mutations can also produce new traits, such as when mutations to an allele for black hair produce a new allele for white hair. This appearance of new traits is important in evolution.

Genes and inheritance

A section of DNA; the sequence of the plate-like units (nucleotides) in the center carries information.

Genes are pieces of DNA that contain information for the synthesis of ribonucleic acids (RNAs) or polypeptides. Genes are inherited as units, with two parents dividing out copies of their genes to their offspring. Humans have two copies of each of their genes, but each egg or sperm cell only gets one of those copies for each gene. An egg and sperm join to form a zygote with a complete set of genes. The resulting offspring has the same number of genes as their parents, but for any gene, one of their two copies comes from their father and one from their mother.

Example of mixing

The effects of mixing depend on the types (the alleles) of the gene. If the father has two copies of an allele for red hair, and the mother has two copies for brown hair, all their children get the two alleles that give different instructions, one for red hair and one for brown. The hair color of these children depends on how these alleles work together. If one allele dominates the instructions from another, it is called the dominant allele, and the allele that is overridden is called the recessive allele. In the case of a daughter with alleles for both red and brown hair, brown is dominant and she ends up with brown hair.

A Punnett square showing how two brown haired parents can have red or brown haired children. 'B' is for brown and 'b' is for red.

Red hair is a recessive trait.

Although the red color allele is still there in this brown-haired girl, it doesn't show. This is a difference between what is seen on the surface (the traits of an organism, called its phenotype) and the genes within the organism (its genotype). In this example, the allele for brown can be called "B" and the allele for red "b". (It is normal to write dominant alleles with capital letters and recessive ones with lower-case letters.) The brown hair daughter has the "brown hair phenotype" but her genotype is Bb, with one copy of the B allele, and one of the b allele.

Now imagine that this woman grows up and has children with a brown-haired man who also has a Bb genotype. Her eggs will be a mixture of two types, one sort containing the B allele, and one sort the b allele. Similarly, her partner will produce a mix of two types of sperm containing one or the other of these two alleles. When the transmitted genes are joined up in their offspring, these children have a chance of getting either brown or red hair, since they could get a genotype of BB = brown hair, Bb = brown hair or bb = red hair. In this generation, there is, therefore, a chance of the recessive allele showing itself in the phenotype of the children—some of them may have red hair like their grandfather.

Many traits are inherited in a more complicated way than the example above. This can happen when there are several genes involved, each contributing a small part to the result. Tall people tend to have tall children because their children get a package of many alleles that each contribute a bit to how much they grow. However, there are not clear groups of "short people" and "tall people", like there are groups of people with brown or red hair. This is because of the large number of genes involved; this makes the trait very variable and people are of many different heights. Despite a common misconception, the green/blue eye traits are also inherited in this complex inheritance model. Inheritance can also be complicated when the trait depends on the interaction between genetics and environment. For example, malnutrition does not change traits like eye color, but can stunt growth.

How genes work

Genes make proteins

Main article: Genetic code

The function of genes is to provide the information needed to make molecules called proteins in cells. Cells are the smallest independent parts of organisms: the human body contains about 100 trillion cells, while very small organisms like bacteria are just a single cell. A cell is like a miniature and very complex factory that can make all the parts needed to produce a copy of itself, which happens when cells divide. There is a simple division of labor in cells—genes give instructions and proteins carry out these instructions, tasks like building a new copy of a cell, or repairing the damage. Each type of protein is a specialist that only does one job, so if a cell needs to do something new, it must make a new protein to do this job. Similarly, if a cell needs to do something faster or slower than before, it makes more or less of the protein responsible. Genes tell cells what to do by telling them which proteins to make and in what amounts.

Genes are expressed by being transcribed into RNA, and this RNA then translated into protein.

Proteins are made of a chain of 20 different types of amino acid molecules. This chain folds up into a compact shape, rather like an untidy ball of string. The shape of the protein is determined by the sequence of amino acids along its chain and it is this shape that, in turn, determines what the protein does. For example, some proteins have parts of their surface that perfectly match the shape of another molecule, allowing the protein to bind to this molecule very tightly. Other proteins are enzymes, which are like tiny machines that alter other molecules.

The information in DNA is held in the sequence of the repeating units along the DNA chain. These units are four types of nucleotides (A, T, G and C) and the sequence of nucleotides stores information in an alphabet called the genetic code. When a gene is read by a cell the DNA sequence is copied into a very similar molecule called RNA (this process is called transcription). Transcription is controlled by other DNA sequences (such as promoters), which show a cell where genes are, and control how often they are copied. The RNA copy made from a gene is then fed through a structure called a ribosome, which translates the sequence of nucleotides in the RNA into the correct sequence of amino acids and joins these amino acids together to make a complete protein chain. The new protein then folds up into its active form. The process of moving information from the language of RNA into the language of amino acids is called translation.

DNA replication. DNA is unwound and nucleotides are matched to make two new strands.

If the sequence of the nucleotides in a gene changes, the sequence of the amino acids in the protein it produces may also change—if part of a gene is deleted, the protein produced is shorter and may not work anymore. This is the reason why different alleles of a gene can have different effects on an organism. As an example, hair color depends on how much of a dark substance called melanin is put into the hair as it grows. If a person has a normal set of the genes involved in making melanin, they make all the proteins needed and they grow dark hair. However, if the alleles for a particular protein have different sequences and produce proteins that can't do their jobs, no melanin is produced and the person has white skin and hair (albinism).

Genes are copied

Main article: DNA replication

Genes are copied each time a cell divides into two new cells. The process that copies DNA is called DNA replication. It is through a similar process that a child inherits genes from its parents when a copy from the mother is mixed with a copy from the father.

DNA can be copied very easily and accurately because each piece of DNA can direct the assembly of a new copy of its information. This is because DNA is made of two strands that pair together like the two sides of a zipper. The nucleotides are in the center, like the teeth in the zipper, and pair up to hold the two strands together. Importantly, the four different sorts of nucleotides are different shapes, so for the strands to close up properly, an A nucleotide must go opposite a T nucleotide, and a G opposite a C. This exact pairing is called base pairing.

When DNA is copied, the two strands of the old DNA are pulled apart by enzymes; then they pair up with new nucleotides and then close. This produces two new pieces of DNA, each containing one strand from the old DNA and one newly made strand. This process is not predictably perfect as proteins attach to a nucleotide while they are building and cause a change in the sequence of that gene. These changes in the DNA sequence are called mutations. Mutations produce new alleles of genes. Sometimes these changes stop the functioning of that gene or make it serve another advantageous function, such as the melanin genes discussed above. These mutations and their effects on the traits of organisms are one of the causes of evolution.

Genes and evolution

Further information: Introduction to evolution, History of evolutionary thought, and Evolutionary developmental biology

Mice with different coat colors

A population of organisms evolves when an inherited trait becomes more common or less common over time. For instance, all the mice living on an island would be a single population of mice: some with white fur, some gray. If over generations, white mice became more frequent and gray mice less frequent, then the color of the fur in this population of mice would be evolving. In terms of genetics, this is called an increase in allele frequency.

Alleles become more or less common either by chance in a process called genetic drift or by natural selection. In natural selection, if an allele makes it more likely for an organism to survive and reproduce, then over time this allele becomes more common. But if an allele is harmful, natural selection makes it less common. In the above example, if the island were getting colder each year and snow became present for much of the time, then the allele for white fur would favor survival since predators would be less likely to see them against the snow, and more likely to see the gray mice. Over time white mice would become more and more frequent, while gray mice less and less.

Mutations create new alleles. These alleles have new DNA sequences and can produce proteins with new properties. So if an island was populated entirely by black mice, mutations could happen creating alleles for white fur. The combination of mutations creating new alleles at random, and natural selection picking out those that are useful, causes an adaptation. This is when organisms change in ways that help them to survive and reproduce. Many such changes, studied in evolutionary developmental biology, affect the way the embryo develops into an adult body.

Inherited diseases

Some diseases are hereditary and run in families; others, such as infectious diseases, are caused by the environment. Other diseases come from a combination of genes and the environment. Genetic disorders are diseases that are caused by a single allele of a gene and are inherited in families. These include Huntington's disease, cystic fibrosis or Duchenne muscular dystrophy. Cystic fibrosis, for example, is caused by mutations in a single gene called CFTR and is inherited as a recessive trait.

Other diseases are influenced by genetics, but the genes a person gets from their parents only change their risk of getting a disease. Most of these diseases are inherited in a complex way, with either multiple genes involved, or coming from both genes and the environment. As an example, the risk of breast cancer is 50 times higher in the families most at risk, compared to the families least at risk. This variation is probably due to a large number of alleles, each changing the risk a little bit. Several of the genes have been identified, such as BRCA1 and BRCA2, but not all of them. However, although some of the risks are genetic, the risk of this cancer is also increased by being overweight, heavy alcohol consumption and not exercising. A woman's risk of breast cancer, therefore, comes from a large number of alleles interacting with her environment, so it is very hard to predict.

Genetic engineering

Main article: Genetic engineering

Since traits come from the genes in a cell, putting a new piece of DNA into a cell can produce a new trait. This is how genetic engineering works. For example, rice can be given genes from a maize and a soil bacteria so the rice produces beta-carotene, which the body converts to vitamin A. This can help children with Vitamin A deficiency. Another gene being put into some crops comes from the bacterium Bacillus thuringiensis; the gene makes a protein that is an insecticide. The insecticide kills insects that eat the plants but is harmless to people. In these plants, the new genes are put into the plant before it is grown, so the genes are in every part of the plant, including its seeds. The plant's offspring inherit the new genes, which has led to concern about the spread of new traits into wild plants.

The kind of technology used in genetic engineering is also being developed to treat people with genetic disorders in an experimental medical technique called gene therapy. However, here the new, properly working gene is put in targeted cells, not altering the chance of future children inheriting the disease causing alleles.

Transcortical sensory aphasia

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Transcortical_sensory_aphasia

Transcortical sensory aphasia (TSA) is a kind of aphasia that involves damage to specific areas of the temporal lobe of the brain, resulting in symptoms such as poor auditory comprehension, relatively intact repetition, and fluent speech with semantic paraphasias present. TSA is a fluent aphasia similar to Wernicke's aphasia (receptive aphasia), with the exception of a strong ability to repeat words and phrases. The person may repeat questions rather than answer them ("echolalia").

In all of these ways, TSA is very similar to a more commonly known language disorder, receptive aphasia. However, transcortical sensory aphasia differs from receptive aphasia in that patients still have intact repetition and exhibit echolalia, or the compulsive repetition of words. Transcortical sensory aphasia cannot be diagnosed through brain imaging techniques such as functional magnetic resonance imaging (fMRI), as the results are often difficult to interpret. Therefore, clinicians rely on language assessments and observations to determine if a patient presents with the characteristics of TSA. Patients diagnosed with TSA have shown partial recovery of speech and comprehension after beginning speech therapy. Speech therapy methods for patients with any subtype of aphasia are based on the principles of learning and neuroplasticity. Clinical research on TSA is limited because it occurs so infrequently in patients with aphasia that it is very difficult to perform systematic studies.

TSA should not be confused with transcortical motor aphasia (TMA), which is characterized by nonfluent speech output, with good comprehension and repetition. Patients with TMA have impaired writing skills, difficulty speaking and difficulty maintaining a clear thought process. Furthermore, TMA is caused by lesions in cortical motor areas of the brain as well as lesions in the anterior portion of the basal ganglia, and can be seen in patients with expressive aphasia.

Affected brain areas

Damage to the inferior left temporal lobe, which is shown in green, is associated with TSA.

Transcortical sensory aphasia is caused by lesions in the inferior left temporal lobe of the brain located near Wernicke's area, and is usually due to minor hemorrhage or contusion in the temporal lobe, or infarcts of the left posterior cerebral artery (PCA). One function of the arcuate fasciculus is the connection between Wernicke’s and Broca’s area. In TSA Wernicke’s and Broca’s areas are spared, meaning that lesions do not occur in these regions of the brain. However, since the arcuate fasciculus, Wernicke's area, and Broca's area are secluded from the rest of the brain in TSA, patients still have intact repetition (as information from the arcuate fasciculus is relayed to Broca’s area), but cannot attach meaning to words, either spoken or heard.

Characteristics

Transcortical sensory aphasia is characterized as a fluent aphasia. Fluency is determined by direct qualitative observation of the patient’s speech to determine the length of spoken phrases, and is usually characterized by a normal or rapid rate; normal phrase length, rhythm, melody, and articulatory agility; and normal or paragrammatic speech. Transcortical sensory aphasia is a disorder in which there is a discrepancy between phonological processing, which remains intact, and lexical-semantic processing, which is impaired.^[6] Therefore, patients can repeat complicated phrases, however they lack comprehension and propositional speech. This disconnect occurs since Wernicke’s area is not damaged in patients with TSA, therefore repetition is spared while comprehension is affected. Patients with intact repetition can repeat both simple and complex phrases spoken by others, e.g. when asked if the patient would like to go for a walk, he or she would respond "go for walk." Although patients can respond appropriately, due to the extent of their TSA, it is most likely that they do not comprehend what others ask them. In addition to problems in comprehension, transcortical sensory aphasia is further characterized based on deficits in naming and paraphasia.

Verbal comprehension

Impaired verbal comprehension can be the result a number of causes such as failure of speech sound discrimination, word recognition, auditory working memory, or syntactic structure building. When clinically examined, patients with TSA will exhibit poor comprehension of verbal commands. Based on the extent of the comprehension deficiency, patients will have difficulty following simple commands, e.g. “close your eyes.” Depending on the extent of affected brain area, patients are able to follow simple commands but may not be able to comprehend more difficult, multistep commands, e.g. “point to the ceiling, then touch your left ear with your right hand." Verbal commands as such, that require the patient to cross over the midline of their body are typically more taxing than commands that involve solely the right or left side. When increasing the complexity of verbal commands comprehension is often tested by varying the grammatical structure of the command to determine whether or not the patient understands different grammatical variations of the same sentence. Commands involving the passive voice or possessive, e.g. "If the snake killed the mouse, which one is still alive," usually result in comprehension problems in those who can understand simple questions.

Naming

Naming involves the ability to recall an object. Patients with TSA, as well as patients with all other aphasia subtypes, exhibit poor naming. Clinical assessment of naming involves the observer first asking the patient to name high frequency objects such as clock, door, and chair. TSA patients who name common objects with ease generally have difficulty naming both uncommon objects and specific parts of objects such as lapel, or the dial on a watch.

Paraphasia

Patients with TSA typically exhibit paraphasia; their speech is fluent but often error-prone. Their speech is often unintelligible as they tend to use the wrong words, e.g. tree instead of train or uses words in senseless and incorrect combinations.

Diagnosis

Clinical assessment

Sensory aphasia is typically diagnosed by non-invasive evaluations. Neurologists, neuropsychologists or speech pathologists will administer oral evaluations to determine the extent of a patient’s comprehension and speech capability. Initial assessment will determine if the cause of linguistic deficiency is aphasia. If the diagnosis is then confirmed, testing will next address the type of aphasia and its severity. The Boston Diagnostic Aphasia Examination specializes in determining the severity of a sensory aphasia through the observation of conversational behaviors. Several modalities of perception and response are observed in conjunction with the subject’s ability to process sensory information. The location of the brain lesion and type of the aphasia can then be inferred from the observed symptoms. The Minnesota Test for Differential Diagnosis is the most lengthy and thorough assessment of sensory aphasia. It pinpoints weaknesses in the auditory and visual senses, as well as reading comprehension. From this differential diagnosis, a patient’s course of treatment can be determined. After treatment planning, the Porch Index of Communicative Ability is used to evaluate prognosis and the degree of recovery.

Imaging

fMRI is a measure of the increase in blood flow to localized areas of the brain that coincide with neural activity and is used to image brain activity related to a specific task or sensory process. It is a commonly used method for imaging brain activity in aphasia patients.

Sensory aphasia cannot be diagnosed through the use of imaging techniques. Differences in cognition between asymptomatic subjects and affected patients can be observed via functional magnetic resonance imaging (fMRI). However, these results only reveal temporal differences in cognition between control and diagnosed subjects. The degree of progression during therapy can also be surveyed through cognition tests monitored by fMRI. Many patients’ progress is assessed over time via repeated testing and corresponding cerebral imaging by fMRI.

Management

Due to advances in modern neuroimaging, scientists have been able to gain a better understanding of how language is learned and comprehended. Based on the new data from the world of neuroscience, improvements can be made in coping with the disorder.

Therapists have been developing multiple methods of improving speech and comprehension. These techniques utilize three general principles: maximizing therapy occurrences, ensuring behavioral and communicative relevance, and allowing patients to focus on the language tools that are still available in his or her repertoire.

Many of the following treatment techniques are used to improve auditory comprehension in patients with aphasia:

• Using common words
• Using concrete nouns is more effective than using adjectives, adverbs, or verbs
• Using action verbs that are easily imagined
• Concise and grammatically simple sentences as opposed to lengthy sentences
• Speaking slowly, repeating oneself several times when conversing with aphasic patients
• Using gestures

A relatively new method of language therapy involves coincidence learning. Coincidence learning focuses on the simultaneous learning of two or more events and stipulates that these events are wired together in the brain, strengthening the learning process. Therapists use coincidence learning to find and improve language correlations or coincidences that have been either damaged or deleted by severe cases of aphasia, such as transcortical sensory aphasia. This technique is important in brain function and recovery, as it strengthens associated brain areas that remain unaffected after brain damage. It can be achieved with intensive therapy hours in order to maximize time where correlation is emphasized.

Through careful analysis of neuroimaging studies, a correlation has been developed with motor function and the understanding of action verbs. For example, leg and motor areas were seen to be activated words such as "kick", leading scientists to understand the connection between motor and language processes in the brain. This is yet another example of using relationships that are related in the brain for the purpose of rehabilitating speech and comprehension.

Of huge importance in aphasia therapy is the need to start practicing as soon as possible.^{[citation needed]} Greater recovery occurs when a patient attempts to improve their comprehension and speaking soon after aphasia occurs. There is an inverse relationship between the length of time spent not practicing and level of recovery. The patient should be pushed to their limits of verbal communication in order for them to practice and build upon their remaining language skills.

One effective therapy technique is using what are known as language games in order to encourage verbal communication. One famous example is known as "Builder's Game", where a 'builder' and a 'helper' must communicate in order to effectively work on a project. The helper must hand the builder the tools he or she may need, which requires effective oral communication. The builder succeeds by requesting tools from the assistant by usually using single word utterances, such as 'hammer' or 'nail'. Thus, when the helper hands the tool to the builder, the game incorporates action with language, a key therapy technique. The assistant would then hand the builder the requested tool. Success of the game occurs when the builder's requests are specific to ensure successful building.

Ultimately, regardless of therapy plan or method, improvement in speech does not appear overnight; it requires a significant time investment by the patient as well as a dedicated speech therapist seeking to ensure that the patient is focusing on the correct speech tasks outside of the clinic. Furthermore, the patient must collaborate with friends and family members during their free time in order to maximize the efficacy of the treatment.

Primary progressive aphasia

From Wikipedia, the free encyclopedia

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

 

Primary progressive aphasia
Regions of the left hemisphere that can give rise to aphasia when damaged.

In neuropathy, primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. As with other types of aphasia, the symptoms that accompany PPA depend on what parts of the brain's left hemisphere are significantly damaged. However, unlike most other aphasias, PPA results from continuous deterioration in brain tissue, which leads to early symptoms being far less detrimental than later symptoms.

Those with PPA slowly lose the ability to speak, write, read, and generally comprehend language. Eventually, almost every patient becomes mute and completely loses the ability to understand both written and spoken language. Although it was first described as solely impairment of language capabilities while other mental functions remain intact, it is now recognized that many, if not most of those with PPA experience impairment of memory, short-term memory formation and loss of executive functions.

It was first described as a distinct syndrome by M. Marsel Mesulam in 1982. PPAs have a clinical and pathological overlap with the frontotemporal lobar degeneration spectrum of disorders and Alzheimer's disease. Unlike those affected by Alzheimer's, people with PPA are generally able to maintain self-sufficiency.

Causes

Currently, the specific causes for PPA and other degenerative brain disease similar to PPA are viewed as idiopathic (unknown). Autopsies have revealed a variety of brain abnormalities in people who had PPA. These autopsies, as well as imaging techniques such as CT scans, MRI, EEG, single photon emission computed tomography, and positron emission tomography, have generally revealed abnormalities to be almost exclusively in the left hemisphere.

Risk factors

There have been no large epidemiological studies on the incidence and prevalence of the PPA variants. Though it most likely has been underestimated, onset of PPA has been found to occur in the sixth or seventh decade.

There are no known environmental risk factors for the progressive aphasias. However, one observational, retrospective study suggested that vasectomy could be a risk factor for PPA in men. These results have yet to be replicated or demonstrated by prospective studies.

PPA is not considered a hereditary disease. However, relatives of a person with any form of frontotemporal lobar degeneration (FTLD), including PPA, are at slightly greater risk of developing PPA or another form of the condition. In a quarter of patients diagnosed with PPA, there is a family history of PPA or one of the other disorders in the FTLD spectrum of disorders. It has been found that genetic predisposition varies among the different PPA variants, with progressive nonfluent aphasia (PNFA) being more commonly familial in nature than semantic dementia (SD).

The most convincing genetic basis of PPA has been found to be a mutation in the GRN gene. Most patients with observed GRN mutations present clinical features of PNFA, but the phenotype can be atypical.

Diagnosis

Diagnostic criteria

The following diagnosis criteria were defined by Mesulam:

• As opposed to having followed trauma to the brain, a patient must show an insidious onset and a gradual progression of aphasia, defined as a disorder of sentence and/or word usage, affecting the production and comprehension of speech.
• The disorder in question must be the only determinant on functional impairment in the activities of the patient's daily living.
• On the basis of diagnostic procedures, the disorder in question must be unequivocally attributed to a neurodegenerative process.

Whether or not PPA and other aphasias are the only source of cognitive impairment in a patient is often difficult to assess because: 1) as with other neurologically degenerative diseases, such as Alzheimer's disease, there are currently no reliable non-invasive diagnostic tests for aphasias, and thus neuropsychological assessments are the only tool physicians have for diagnosing patients; and 2) aphasias often affect other, non-language portions of these neuropsychological tests, such as those specific for memory.

Classification

In 2011, the classification of primary progressive aphasia was updated to include three clinical variants. Patients must first be diagnosed with PPA, and then divided into variants based on speech production features, repetition, single- word and syntax comprehension, confrontation naming, semantic knowledge, and reading/spelling. In the classical Mesulam criteria for primary progressive aphasia, there are two variants: a non-fluent type PNFA and a fluent type SD.

A third variant of primary progressive aphasia, LPA was then added, and is an atypical form of Alzheimer's disease. For PNFA, the core criteria for diagnosis include agrammatism and slow and labored speech. Inconsistent speech sound errors are also very common, including distortions, deletions, and insertions. In terms of comprehension, there are deficits in syntax and sentence comprehension due to grammatical complexity, but single- word and object comprehension is relatively maintained.

The second variant, SD, presents with deficits in single-word and object comprehension. Naming impairments can be severe, specially for low-frequency objects, and can eventually lead to a more widespread semantic memory deficiency over time. The ability to read and write can also be impaired if there are irregularities between pronunciation and spelling. However, repetition and motor speech is relatively preserved.

The logopenic variant involves impairments in word retrieval, sentence repetition, and phonological paraphasias, comparable to conduction aphasia. Compared to the semantic variant, single word comprehension and naming is spared, however, sentence comprehension presents difficulty because of length and grammatical complexity. Speech will include incomplete words, hesitations preceding content words, and repetition. However, these PPA subtypes differ from similar aphasias, as these subtypes do not occur acutely following trauma to the brain, such as following a stroke, due to differing functional and structural neuroanatomical patterns of involvement and the progressive nature of the disease.

Unlike those affected by Alzheimer's, people with PPA are generally able to maintain the ability to care for themselves, remain employed, and pursue interests and hobbies. Moreover, in diseases such as Alzheimer's disease, Pick's disease, and Creutzfeldt–Jakob disease, progressive deterioration of comprehension and production of language is just one of the many possible types of mental deterioration, such as the progressive decline of memory, motor skills, reasoning, awareness, and visuospatial skills.

Treatment

Due to the progressive, continuous nature of the disease, improvement over time seldom occurs in patients with PPA as it often does in patients with aphasias caused by trauma to the brain.

In terms of medical approaches to treating PPA, there are currently no drugs specifically used for patients with PPA, nor are there any specifically designed interventions for PPA. A large reason for this is the limited research that has been done on this disease. However, in some cases, patients with PPA are prescribed the same drugs Alzheimer's patients are normally prescribed.

The primary approach to treating PPA has been with behavioral treatment, with the hope that these methods can provide new ways for patients to communicate in order to compensate for their deteriorated abilities. Speech therapy can assist an individual with strategies to overcome difficulties. There are three very broad categories of therapy interventions for aphasia: restorative therapy approaches, compensatory therapy approaches, and social therapy approaches. Examples include word retrieval therapy and script training, communication partner training and group therapy.

Rapid and sustained improvement in speech and dementia in a patient with primary progressive aphasia utilizing off-label perispinal etanercept, an anti-TNF treatment strategy also used for Alzheimer's, has been reported. A video depicting the patient's improvement was published in conjunction with the print article. These findings have not been independently replicated and remain controversial.

History

M. Marsel Mesulam coined the term primary progressive aphasia.

Motor neuron diseases

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Motor_neuron_diseases

 

Motor neuron disease
spinal diagram

Motor neuron diseases or motor neurone diseases (MNDs) are a group of rare neurodegenerative disorders that selectively affect motor neurons, the cells which control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP), pseudobulbar palsy, progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA) and monomelic amyotrophy (MMA), as well as some rarer variants resembling ALS.

Motor neuron diseases affect both children and adults. While each motor neuron disease affects patients differently, they all cause movement-related symptoms, mainly muscle weakness. Most of these diseases seem to occur randomly without known causes, but some forms are inherited. Studies into these inherited forms have led to discoveries of various genes (e.g. SOD1) that are thought to be important in understanding how the disease occurs.

Symptoms of motor neuron diseases can be first seen at birth or can come on slowly later in life. Most of these diseases worsen over time; while some, such as ALS, shorten one's life expectancy, others do not. Currently, there are no approved treatments for the majority of motor neuron disorders, and care is mostly symptomatic.

Signs and symptoms

A man with amyotrophic lateral sclerosis (ALS). (A) He needs assistance to stand. (B) Advanced atrophy of the tongue. (C) There is upper limb and truncal muscle atrophy with a positive Babinski sign. (D) Advanced thenar muscle atrophy.

Signs and symptoms depend on the specific disease, but motor neuron diseases typically manifest as a group of movement-related symptoms. They come on slowly, and worsen over the course of more than three months. Various patterns of muscle weakness are seen, and muscle cramps and spasms may occur. One can have difficulty breathing with climbing stairs (exertion), difficulty breathing when lying down (orthopnea), or even respiratory failure if breathing muscles become involved. Bulbar symptoms, including difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and excessive saliva production (sialorrhea), can also occur. Sensation, or the ability to feel, is typically not affected. Emotional disturbance (e.g. pseudobulbar affect) and cognitive and behavioural changes (e.g. problems in word fluency, decision-making, and memory) are also seen. There can be lower motor neuron findings (e.g. muscle wasting, muscle twitching), upper motor neuron findings (e.g. brisk reflexes, Babinski reflex, Hoffman's reflex, increased muscle tone), or both.

Motor neuron diseases are seen both in children and adults. Those that affect children tend to be inherited or familial, and their symptoms are either present at birth or appear before learning to walk. Those that affect adults tend to appear after age 40. The clinical course depends on the specific disease, but most progress or worsen over the course of months. Some are fatal (e.g. ALS), while others are not (e.g. PLS).

Patterns of weakness

Various patterns of muscle weakness occur in different motor neuron diseases. Weakness can be symmetric or asymmetric, and it can occur in body parts that are distal, proximal, or both. According to Statland et al., there are three main weakness patterns that are seen in motor neuron diseases, which are:

1. Asymmetric distal weakness without sensory loss (e.g. ALS, PLS, PMA, MMA)
2. Symmetric weakness without sensory loss (e.g. PMA, PLS)
3. Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement; e.g. ALS, PBP, PLS)

Lower and upper motor neuron findings

Motor neuron diseases are on a spectrum in terms of upper and lower motor neuron involvement. Some have just lower or upper motor neuron findings, while others have a mix of both. Lower motor neuron (LMN) findings include muscle atrophy and fasciculations, and upper motor neuron (UMN) findings include hyperreflexia, spasticity, muscle spasm, and abnormal reflexes.

Pure upper motor neuron diseases, or those with just UMN findings, include PLS.

Pure lower motor neuron diseases, or those with just LMN findings, include PMA.

Motor neuron diseases with both UMN and LMN findings include both familial and sporadic ALS.

Causes

Most cases are sporadic and their causes are usually not known. It is thought that environmental, toxic, viral, or genetic factors may be involved.

DNA damage

TAR DNA-binding protein 43 (TDP-43), is a critical component of the non-homologous end joining (NHEJ) enzymatic pathway that repairs DNA double-strand breaks in pluripotent stem cell-derived motor neurons. TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the XRCC4-DNA ligase protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ALS patients' spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ.

Associated risk factors

In adults, men are more commonly affected than women.

Diagnosis

Differential diagnosis can be challenging due to the number of overlapping symptoms, shared between several motor neuron diseases. Frequently, the diagnosis is based on clinical findings (i.e. LMN vs. UMN signs and symptoms, patterns of weakness), family history of MND, and a variation of tests, many of which are used to rule out disease mimics, which can manifest with identical symptoms.

Classification

Corticospinal tract. Upper motor neurons originating in the primary motor cortex synapse to either lower motor neurons in the anterior horn of the central gray matter of the spinal cord (insert) or brainstem motor neurons (not shown). Motor neuron disease can affect either upper motor neurons (UMNs) or lower motor neurons (LMNs).

Motor neuron disease describes a collection of clinical disorders, characterized by progressive muscle weakness and the degeneration of the motor neuron on electrophysiological testing. The term "motor neuron disease" has varying meanings in different countries. Similarly, the literature inconsistently classifies which degenerative motor neuron disorders can be included under the umbrella term "motor neuron disease". The four main types of MND are marked (*) in the table below.

All types of MND can be differentiated by two defining characteristics:

1. Is the disease sporadic or inherited?
2. Is there involvement of the upper motor neurons (UMN), the lower motor neurons (LMN), or both?

Sporadic or acquired MNDs occur in patients with no family history of degenerative motor neuron disease. Inherited or genetic MNDs adhere to one of the following inheritance patterns: autosomal dominant, autosomal recessive, or X-linked. Some disorders, like ALS, can occur sporadically (85%) or can have a genetic cause (15%) with the same clinical symptoms and progression of disease.

UMNs are motor neurons that project from the cortex down to the brainstem or spinal cord. LMNs originate in the anterior horns of the spinal cord and synapse on peripheral muscles. Both motor neurons are necessary for the strong contraction of a muscle, but damage to an UMN can be distinguished from damage to a LMN by physical exam.

Type	UMN degeneration	LMN degeneration
Sporadic MNDs
Sporadic amyotrophic lateral sclerosis (ALS)*	Yes	Yes
Primary lateral sclerosis (PLS)*	Yes	No
Progressive muscular atrophy (PMA)*	No	Yes
Progressive bulbar palsy (PBP)*	Yes	Yes, bulbar region
Pseudobulbar palsy	Yes, bulbar region	No
Monomelic amyotrophy (MMA)	No	Yes
Inherited MNDs
Familial amyotrophic lateral sclerosis (ALS)*	Yes	Yes

Tests

• Cerebrospinal fluid (CSF) tests: Analysis of the fluid from around the brain and spinal cord could reveal signs of an infection or inflammation.
• Magnetic resonance imaging (MRI): An MRI of the brain and spinal cord is recommended in patients with UMN signs and symptoms to explore other causes, such as a tumor, inflammation, or lack of blood supply (stroke).
• Electromyogram (EMG) & nerve conduction study (NCS): The EMG, which evaluates muscle function, and NCS, which evaluates nerve function, are performed together in patients with LMN signs.
• For patients with MND affecting the LMNs, the EMG will show evidence of: (1) acute denervation, which is ongoing as motor neurons degenerate, and (2) chronic denervation and reinnervation of the muscle, as the remaining motor neurons attempt to fill in for lost motor neurons.
• By contrast, the NCS in these patients is usually normal. It can show a low compound muscle action potential (CMAP), which results from the loss of motor neurons, but the sensory neurons should remain unaffected.
• Tissue biopsy: Taking a small sample of a muscle or nerve may be necessary if the EMG/NCS is not specific enough to rule out other causes of progressive muscle weakness, but it is rarely used.

Treatment

There are no known curative treatments for the majority of motor neuron disorders. Physiotherapy helps maintain movement and function when someone is affected by disability, injury or illness. This is achieved through movement and exercise, manual therapy, education and advice. Although physiotherapy can’t reverse the effects of MND, or Kennedy’s disease, it can help maintain range of movement and comfort for as long as possible.

Prognosis

The table below lists life expectancy for patients who are diagnosed with MND.

Type	Median survival time from start of symptoms
Amyotrophic lateral sclerosis (ALS)	2–5 years
Primary lateral sclerosis (PLS)	8–10 years
Progressive muscular atrophy (PMA)	2–4 years
Progressive bulbar palsy (PBP)	6 months – 3 years
Pseudobulbar palsy	No change in survival

Terminology

In the United States and Canada, the term motor neuron disease usually refers to the group of disorders while amyotrophic lateral sclerosis is frequently called Lou Gehrig's disease. In the United Kingdom and Australia, the term motor neuron(e) disease is used for amyotrophic lateral sclerosis, although is not uncommon to refer to the entire group.

While MND refers to a specific subset of similar diseases, there are numerous other diseases of motor neurons that are referred to collectively as "motor neuron disorders", for instance the diseases belonging to the spinal muscular atrophies group. However, they are not classified as "motor neuron diseases" by the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), which is the definition followed in this article.