Dyslexia future or investigational therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Future or Investigational Therapies

Scientific Research

Theories of Developmental Dyslexia

The following theories should not be viewed as competing, but viewed as theories trying to explain the underlying causes of a similar set of symptoms from a variety of research perspectives and backgrounds.

The Evolutionary Hypothesis

This theory posits that reading is an unnatural act, and carried out by humans for an exceedingly brief period in our evolutionary history (Dalby, 1986). It has been less than a hundred years that most western societies promoted reading by the mass population and therefore the forces that shape our behavior have been weak. Many areas of the world still do not have access to reading for the majority of the population. There is no evidence that "pathology" underlies dyslexia but much evidence for cerebral variation or differences. It is these essential differences that are taxed with the artificial task of reading.

The Phonological Hypothesis

The phonological hypothesis postulates that dyslexics have a specific impairment in the representation, storage and/or retrieval of speech sounds. It explains dyslexics' reading impairment on the basis that learning to read an alphabetic system requires learning the grapheme/phoneme correspondence, i.e. the correspondence between letters and constituent sounds of speech. If these sounds are poorly represented, stored or retrieved, the learning of grapheme/phoneme correspondences, the foundation of reading by phonic methods for alphabetic systems, will be affected accordingly.

The Rapid Auditory Processing Theory

The rapid auditory processing theory is an alternative to the phonological deficit theory, which specifies that the primary deficit lies in the perception of short or rapidly varying sounds. Support for this theory arises from evidence that dyslexics show poor performance on a number of auditory tasks, including frequency discrimination and temporal order judgment. Backward masking tasks, in particular, demonstrate a 100-fold (40 dB) difference in sensitivity between normals and dyslexics. Abnormal neurophysiological responses to various auditory stimuli have also been demonstrated. The failure to correctly represent short sounds and fast transitions would cause further difficulties in particular when such acoustic events are the cues to phonemic contrasts, as in /ba/ versus /da/. There is also evidence that dyslexics may have poorer categorical perception of certain contrasts.

The Visual Theory

The visual theory (Lovegrove et al., 1980; Livingstone et al., 1991; Stein and Walsh, 1997) reflects another long standing tradition in the study of dyslexia, that of considering it as a visual impairment giving rise to difficulties with the processing of letters and words on a page of text. This may take the form of unstable binocular fixations, poorvergence, or increased visual crowding. The visual theory does not exclude a phonological deficit, but emphasizes a visual contribution to reading problems, at least in some dyslexic individuals. At the biological level, the proposed aetiology of the visual dysfunction is based on the division of the visual system into two distinct pathways that have different roles and properties: the magnocellular and parvocellular pathways. The theory postulates that the magnocellular pathway is selectively disrupted in certain dyslexic individuals, leading to deficiencies in visual processing, and, via the posterior parietal cortex, to abnormal binocular control and visuospatial attention. Evidence for magnocellular dysfunction comes from anatomical studies showing abnormalities of the magnocellular layers of the lateral geniculate nucleus (Livingstone et al., 1991), psychophysical studies showing decreased sensitivity in the magnocellular range, i.e. low spatial frequencies and high temporal frequencies in dyslexics, and brain imaging studies.

The Cerebellar Theory

Yet another view is represented by the automaticity/ cerebellar theory of dyslexia. Here the biological claim is that the dyslexic's cerebellum is mildly dysfunctional and that a number of cognitive difficulties ensue. First, the cerebellum plays a role in motor control and therefore in speech articulation. It is postulated that retarded or dysfunctional articulation would lead to deficient phonological representations. Secondly, the cerebellum plays a role in the automatization of overlearned tasks, such as driving, typing and reading. A weak capacity to automatize would affect, among other things, the learning of grapheme±phoneme correspondences. Support for the cerebellar theory comes from evidence of poor performance of dyslexics in a large number of motor tasks, in dual tasks demonstrating impaired automatization of balance, and in time estimation, a non-motor cerebellar task. Brain imaging studies have also shown anatomical, metabolic and activation differences in the cerebellum of dyslexics.

The Magnocellular Theory

There is a unifying theory that attempts to integrate all the findings mentioned above. A generalization of the visual theory, the magnocellular theory postulates that the magnocellular dysfunction is not restricted to the visual pathways but is generalized to all modalities (visual and auditory as well as tactile). Furthermore, as the cerebellum receives massive input from various magnocellular systems in the brain, it is also predicted to be affected by the general magnocellular defect (Stein et al., 2001). Through a single biological cause, this theory therefore manages to account for all known manifestations of dyslexia: visual, auditory, tactile, motor and, consequently, phonological. Beyond the evidence pertaining to each of the theories described previously, evidence specifically relevant to the magnocellular theory includes magnocellular abnormalities in the medial as well as the lateral geniculate nucleus of dyslexics' brains, poor performance of dyslexics in the tactile domain, and the co-occurrence of visual and auditory problems in certain dyslexics.

Perceptual Visual-noise Exclusion Hypothesis

The concept of a perceptual noise exclusion (Visual-Noise) deficit is an emerging hypothesis, supported by research showing that dyslexic subjects experience difficulty in performing visual tasks such as motion detection in the presence of perceptual distractions, but do not show the same impairment when the distracting factors are removed in an experimental setting. The researchers have analogized their findings concerning visual discrimination tasks to findings in other research related to auditory discrimination tasks. They assert that dyslexic symptoms arise because of an impaired ability to filter out both visual and auditory distractions, and to categorize information so as to distinguish the important sensory data from the irrelevant.

Research Also Indicates

Genetic Factors

Studies have linked several forms of dyslexia to genetic markers. One major genetic

As of 2007, genetic research in families with dyslexia have identified nine chromosome regions that may be associated with susceptibility to dyslexia. However, several of the major studies have not been replicated.

Physiology

Modern neuroimaging techniques such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) have produced clear evidence of structural differences in the brains of children with reading difficulties. It has been found that people with dyslexia have a deficit in parts of the left hemisphere of the brain involved in reading, which includes the inferior frontal gyrus, inferior parietal lobule, and middle and ventral temporal cortex.

Scientific studies of brains donated to medical research have revealed that there are anatomical differences in two parts of the dyslexic brain: the cerebral cortex and the thalamus. In 1979 Albert Galaburda of Harvard Medical Schoolnoticed anatomical differences in the language center in a dyslexic brain, showing microscopic differences known asectopias and microgyria. Both affect the typical six-layer structure of the cortex. An ectopia is a collection of neurons that have pushed up from the lower layers of the cortex into the outermost one. A microgyrus is an area of cortex that includes only four layers instead of six. These differences affect connectivity and functionality of the cortex in critical areas related to auditory processing andvisual processing, which seems consistent with the hypothesis that dyslexia stems from a phonological awareness deficit.

Studies of both autopsied brains and living brains using neuroimaging techniques have shown that the brains of dyslexic children are symmetrical, unlike the asymmetrical brains of non-dyslexic readers who had larger left hemispheres.

Scientists do not claim that all people with dyslexia have these structural brain differences. However, the studies are evidence that some children's reading problems are brain based. The challenge for researchers is to determine how these structural differences affect reading acquisition.

Effect of Language Orthography

Some studies have concluded that speakers of languages whose orthography has a highly consistent correspondence between letter and sound (e.g., Italian) suffer less from the effects of dyslexia than speakers of languages where the letter-sound correspondence is less consistent (e.g. English and French).

In one of these studies, reported in Seymour et al., the word-reading accuracy of first-grade children of different European languages was measured. English children had an accuracy of just 40%, whereas among children of most other European languages accuracy was about 95%, with French and Danish children somewhere in the middle at about 75%; Danish and French are known to have an irregular pronunciation.

However, this does not mean that dyslexia is caused by orthography: instead, Ziegler et al. claim that the dyslexia suffered by German or Italian dyslexics is of the same kind as the one suffered by the English ones, supporting the theory that the origin of dyslexia is biological. In a study by Paulescu et al. (Science, 2001) English, French, and Italian dyslexics were found to have the same brain function signature when studied with functional magnetic resonance imaging (fMRI), a signature that differed from non-dyslexic readers. However, dyslexia has more pronounced effects on orthographically difficult languages, e.g., dyslexics have more difficulty in English than Italian. Modern theories of some forms of dyslexia uses orthography to test a hypothesis of psychological causation

Characteristics

Formal diagnosis of dyslexia is made by a qualified professional, such as a neurologist or an educational psychologist. Evaluation generally includes testing of reading ability together with measures of underlying skills such as tests of rapid naming, to evaluate short term memory and sequencing skills, and nonword reading to evaluate phonological coding skills. Evaluation will usually also include an IQ test to establish a profile of learning strengths and weaknesses. However, the use of a "discrepancy" between full scale IQ and reading level as a factor in diagnosis has been discredited by recent research. It often includes interdisciplinary testing to exclude other possible causes for reading difficulties, such as a more generalized cognitive impairment or physical causes such as problems with vision or hearing.

Recent advances in neuroimaging and genetics provide evidence that could potentially help identify children with dyslexia before they learn to read in the future. However, such tests have not yet been developed and more research is needed before such testing could be considered reliable.

Speech, Hearing and Listening

Speech delays may be an early warning sign of dyslexia. Many dyslexics may have problems processing and decoding auditory input prior to reproducing their own version of speech. Early stuttering or cluttering can also be warning signs of dyslexia.

Many dyslexics also can have problems with speaking clearly. They can mix up sounds in multi-syllabic words (ex: aminal for animal, bisghetti for spaghetti, hekalopter for helicopter, hangaberg for hamburger, mazageen for magazine, etc.) They also can have problems speaking in full sentences. They can have trouble correctly articulating Rs and Ls as well as Ms and Ns. They often have "immature" speech. They may still be saying "wed and gween" instead of "red and green" in second or third grade. Many dyslexics might have speech therapy in special education. They may have fast speech,cluttered speech, or hesitant speech.

Reading requires the sounding out of words. Therefore, it makes sense that children with speech problems can end up having reading problems later. Many have problems with speech due to problems with auditory processing disorder issues.

Many dyslexics have problems with phonemic awareness. Phonemes are the smallest units in spoken language. The Auditory related underlying causes of dyslexia may be partially remediated by auditory therapy or speech therapy, which help with phonemic awareness. This may help to make sense of phonics which may help with phonological awareness, which is needed to sound out words.

Many acquire auditory processing disorder as an underlying cause of dyslexia from glue ear, otitis media.

Some shared symptoms of the speech/hearing deficits and dyslexia:

1. Confusion with before/after, right/left, and so on
2. Difficulty learning the alphabet
3. Difficulty with word retrieval or naming problems
4. Difficulty identifying or generating rhyming words, or counting syllables in words (phonological awareness)
5. Difficulty with hearing and manipulating sounds in words (phonemic awareness)
6. Difficulty distinguishing different sounds in words (auditory discrimination)
7. Difficulty in learning the sounds of letters
8. Difficulty associating individual words with their correct meanings
9. Difficulty with time keeping and concept of time
10. Confusion with combinations of words
11. Due to fear of speaking incorrectly, some children become withdrawn and shy or become bullies out of their inability to understand the social cues in their environment

Reading and Spelling

• Spelling errors — Because of difficulty learning letter-sound correspondences, individuals with dyslexia might tend to misspell words, or leave vowels out of words.
• Letter order - Dyslexics may also reverse the order of two letters especially when the final, incorrect, word looks similar to the intended word (e.g., spelling "dose" instead of "does").
• Highly phoneticized spelling - Dyslexics also commonly spell words inconsistently, but in a highly phonetic form such as writing "shud" for "should". Dyslexic individuals also typically have difficulty distinguishing among homophones such as "their" and "there".
• Reading — Due to dyslexics' excellent long term memory, young students tend to memorize beginning readers, but are unable to read individual words or phrases.
• Vocabulary - Having a small written vocabulary, even if they have a large spoken vocabulary.

Writing and Motor Skills

Because of literacy problems, an individual with dyslexia may have difficulty with handwriting. This can involve slower writing speed than average or poor handwriting characterised by irregularly formed letters. They may use inappropriate words when writing.

Some studies have also reported gross motor difficulties in dyslexia, including motor skills disorder. This difficulty is indicated by clumsiness and poor coordination. The relationship between motor skills and reading difficulties is poorly understood but could be linked to the role of the cerebellum and inner ear in the development of reading and motor abilities.

Mathematical Abilities

Dyslexia should not be confused with dyscalculia, a learning disability marked by severe difficulties with mathematics. Individuals with dyslexia can be gifted in mathematics while having poor reading skills. However, in spite of this they might have difficulty with word problems (i.e., descriptive mathematics, engineering, or physics problems that rely on written text rather than numbers or formulas). Individuals with dyslexia may also have difficulty remembering mathematical facts, such as multiplication tables, learning the sequence of steps when performing calculations, such as long division, and other mathematics which involve remembering the order in which numbers appear. This may be exhibited by having a slow response in mathematical drills and difficulty with word problems.