Discovery of 42 genome-wide significant loci associated with dyslexia.

Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.

The Association of Dyslexia and Developmental Speech and Language Disorder Candidate Genes with Reading and Language Abilities in Adults.

Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7-73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading.

Single motor unit firing rate after stroke is higher on the less-affected side during stable low-level voluntary contractions.

Muscle weakness is the most common outcome after stroke and a leading cause of adult-acquired motor disability. Single motor unit properties provide insight into the mechanisms of post-stroke motor impairment. Motor units on the more-affected side are reported to have lower peak firing rates, reduced discharge variability and a more compressed dynamic range than healthy subjects. The activity of 169 motor units was discriminated from surface electromyography in 28 stroke patients during sustained voluntary contractions 10% of maximal and compared to 110 units recorded in 16 healthy subjects. Motor units were recorded in three series: ankle dorsiflexion, wrist flexion and elbow flexion. Mean firing rates after stroke were significantly lower on the more-affected than the less-affected side (p < 0.001) with no differences between dominant and non-dominant sides for healthy subjects. When data were combined, firing rates on the less-affected side were significantly higher than those either on the more-affected side or healthy subjects (p < 0.001). Motor unit mean firing rate was higher in the upper-limb than the lower-limb (p < 0.05). The coefficient of variation of motor unit discharge rate was lower for motor units after stroke compared to controls for wrist flexion (p < 0.05) but not ankle dorsiflexion. However the dynamic range of motor units was compressed only for motor units on the more-affected side during wrist flexion. Our results show that the pathological change in motor unit firing rate occurs on the less-affected side after stroke and not the more-affected side as previously reported, and suggest that motor unit behavior recorded in a single muscle after stroke cannot be generalized to muscles acting on other joints even within the same limb. These data emphasize that the less-affected side does not provide a valid control for physiological studies on the more-affected side after stroke and that both sides should be compared to data from age- and sex-matched healthy subjects.

Wii-based movement therapy to promote improved upper extremity function post-stroke: a pilot study.

BACKGROUND: Virtual-reality is increasingly used to improve rehabilitation outcomes. The Nintendo Wii offers an in-expensive alternative to more complex systems. OBJECTIVE: To investigate the efficacy of Wii-based therapy for post-stroke rehabilitation. METHODS: Seven patients (5 men, 2 women, aged 42-83 years; 1-38 months post-stroke, mean 15.3 months) and 5 healthy controls (3 men, 2 women, aged 41-71 years) undertook 1 h of therapy on 10 consecutive weekdays. Patients progressively increased home practice to 3 h per day. RESULTS: Functional ability improved for every patient. The mean performance time significantly decreased per Wolf Motor Function Test task, from 3.2 to 2.8 s, and Fugl-Meyer Assessment scores increased from 42.3 to 47.3. Upper extremity range-of-motion increased by 20.1º and 14.33º for passive and active movements, respectively. Mean Motor Activity Log (Quality of Movement scale) scores increased from 63.2 to 87.5, reflecting a transfer of functional recovery to everyday activities. Balance and dexterity did not improve significantly. No significant change was seen in any of these measures for healthy controls, despite improved skill levels for Wii games. CONCLUSION: An intensive 2-week protocol resulted in significant and clinically relevant improvements in functional motor ability post-stroke. These gains translated to improvement in activities of daily living.