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Biomedical subjects

J F Stein

Publications and source records attributed to J F Stein.

At least 37 records · Page 2Linked to original sources

Selective deficits of vibrotactile sensitivity in dyslexic readers.

Developmental dyslexia is a disability of literacy skill that has also been associated with sensory processing deficits, primarily for the detection of dynamic auditory and visual stimuli. Here we examined whether analogous deficits extend into the domain of somatosensory perception. Detection thresholds for each of three frequencies of vibration were obtained for 11 readers with a prior history of dyslexia and 14 similarly aged adult controls. The poor readers were significantly less sensitive to vibration at 3 Hz (P<0. 01) but not at either 30 or 100 Hz. Detection of each of these three vibration rates is mediated primarily by a separate somatosensory fiber tract; deficits selective to 3 Hz therefore suggest an impairment within the slow-adapting I (SAI) fiber system beginning with Merkel-cell mechanoreceptors in the glabrous skin. Such evidence is compatible with the hypothesis of a generalized, multisensory deficit of temporal processing functions in dyslexia.

Adolescent↗

Dynamic sensory sensitivity and children's word decoding skills.

The relationship between sensory sensitivity and reading performance was examined to test the hypothesis that the orthographic and phonological skills engaged in visual word recognition are constrained by the ability to detect dynamic visual and auditory events. A test battery using sensory psychophysics, psychometric tests, and measures of component literacy skills was administered to 32 unselected 10-year-old primary school children. The results suggest that children's sensitivity to both dynamic auditory and visual stimuli are related to their literacy skills. Importantly, after controlling for intelligence and overall reading ability, visual motion sensitivity explained independent variance in orthographic skill but not phonological ability, and auditory FM sensitivity covaried with phonological skill but not orthographic skill. These results support the hypothesis that sensitivity at detecting dynamic stimuli influences normal children's reading skills. Vision and audition separately may affect the ability to extract orthographic and phonological information during reading.

Acoustic Stimulation↗

Local critical power is an index of local endurance.

The hypothesis that critical power (CP) is significantly lower than the maximal aerobic power of the knee extensors has been tested in nine endurance-trained subjects, seven gymnasts and seven weight lifters. CP was calculated as being equal to the slope of the linear relationship between exhaustion time and work performed at exhaustion on a knee-extension ergometer. CP was compared with the power output at the end of a progressive knee-extension exercise (P(peak)) and the power outputs corresponding to exhaustion times equal to 4 (P(4 min)), 6 (P(6 min)), 8 (P(8 min)) and 10 min (P(10 min)), calculated according to the linear relationship between work and exhaustion time. The hypothesis that CP corresponds to a steady state in metabolic and physiological parameters was tested in the gymnasts and the weight lifters by comparing CP with the fatigue thresholds of the integrated electromyogram (iEMG(FT)), lactate level (La(FT)), oxygen uptake (VO(2FT)) and heart rate (HR(FT)). The results of the present study demonstrate that the value of CP of a local exercise cannot be considered as the equivalent of the maximal aerobic power for general exercises. The values of P(4 min), P(6 min), P(8 min), P(10 min) and P(peak) were significantly higher than CP, and corresponded to 138, 126, 119, 115 and 151% CP, respectively. The results of the present study indicate that CP can be considered as an index of muscular endurance. Indeed, La(FT), iEMG (FT), VO(2FT) and HR(FT) were not significantly different from CP. All of these fatigue thresholds were significantly correlated with CP (r > 0.92). Moreover, the highest coefficient of correlation (r=0.71; P < 0.01) between the percentage of maximal aerobic power in cycling that corresponds to a blood lactate concentration of 4 mmol x l(-1) (OBLA%) and the different local aerobic indices was observed with CP.

Adult↗

Critical power of knee extension exercises does not depend upon maximal strength.

A possible dependence of critical power (CP) and the Y-intercept of the work/exhaustion time relationship (Y(intercept)) on maximal muscular strength of the same muscle group has been studied in nine endurance-trained subjects, seven gymnasts, and seven weight-lifters. CP was calculated as being equal to the slope of the linear relationship between exhaustion time and the work performed at exhaustion on a knee extension ergometer. Y(intercept) was equal to the intercept between this relationship and the work axis. The muscular strength of the knee was evaluated by measuring the torques exerted on a Biodex knee isokinetic dynamometer at four angular velocities: 0 degrees x s(-1) (T0), 90 degrees x s(-1) (T90), 180 degrees x s(-1) (T180) and 240 degrees x s(-1) (T240). The results of the present study do not support the hypothesis that CP depends upon maximal strength. Indeed, CP was not correlated with T0, T90, T180 or T240 (¿r¿ < 0.01). Y(intercept) was significantly and positively correlated only with T90.

Adult↗

Visual motion sensitivity in dyslexia: evidence for temporal and energy integration deficits.

In addition to poor literacy skills, developmental dyslexia has been associated with multisensory deficits for dynamic stimulus detection. In vision these deficits have been suggested to result from impaired sensitivity of cells within the retino-cortical magnocellular pathway and extrastriate areas in the dorsal stream to which they project. One consequence of such selectively reduced sensitivity is a difficulty in extracting motion coherence from dynamic noise, a deficit associated with both developmental dyslexia and persons with extrastriate, dorsal stream lesions. However the precise nature of the mechanism(s) underlying these perceptual deficits in dyslexia remain unknown. In this study, we obtained motion detection thresholds for 10 dyslexic and 10 control adults while varying the spatial and temporal parameters of the random dot kinematogram (RDK) stimuli. In Experiment 1 stimulus duration was manipulated to test whether dyslexics are specifically impaired for detecting short duration, rather than longer stimuli. Dot density was varied in Experiment 2 to examine whether dyslexics' reduced motion sensitivity was affected by the amount of motion energy present in the RDKs. Dyslexics were consistently less sensitive to coherent motion than controls in both experiments. Increasing stimulus duration did not improve dyslexics' performance, whereas increasing dot density did. Thus increasing motion energy assisted the dyslexics, suggesting that their motion detectors have a lower signal to noise ratio, perhaps due to spatial undersampling.

Adult↗

Monocular occlusion can improve binocular control and reading in dyslexics.

Developmental dyslexia is a neurodevelopmental condition which causes 5-10% of children to have unexpected difficulty learning to read. Many dyslexics have impaired development of the magnocellular component of the visual system, which is important for timing visual events and controlling eye movements. Poor control of eye movement may lead to unstable binocular fixation, and hence unsteady vision; this could explain why many dyslexics report that letters appear to move around, causing visual confusion. Previous research has suggested that such binocular confusion can be permanently alleviated by temporarily occluding one eye. The aim of the present study was therefore to assess the binocular control and reading progress of dyslexic children with initially unstable binocular control after the left eye was patched. One hundred and forty-three dyslexics were studied. They were selected from children aged 7-11 years referred to a learning disabilities clinic if they were dyslexic and had unstable binocular control. They were randomly assigned to wear yellow spectacles with or without the left lens occluded, and were followed for 9 months. Significantly more of the children who were given occlusion gained stable binocular fixation in the first 3 months (59%) compared with children given the unoccluded glasses (36%). This advantage was independent of IQ or initial reading ability. Furthermore, at all the 3-month follow-ups, children were more likely to have gained stable binocular control if they had been wearing the occluded glasses. Gaining stable binocular control significantly improved reading. The children who did so with the help of occlusion improved their reading by 9.4 months in the first 3 months, compared with 3.9 months in those who were not patched and did not gain stable fixation. Over the whole 9 months, children who received occlusion and gained stable fixation nearly doubled their rate of progress in reading compared with those who remained unstable. At all the follow-ups the reading of those given occlusion was significantly better than that of those not occluded. Thus monocular occlusion helped children with unstable binocular control to gain good binocular fixation. If they gained stability, they made significantly faster reading progress. The progress made by the children who gained stable fixation was much greater than that achieved with other remedial techniques.

Child↗

Temporary inactivation in the primate motor thalamus during visually triggered and internally generated limb movements.

To better understand the contribution of cerebellar- and basal ganglia-receiving areas of the thalamus [ventral posterolateral nucleus, pars oralis (VPLo), area X, ventral lateral nucleus, pars oralis (VLo), or ventral anterior nucleus, pars parvicellularis (VApc)] to movements based on external versus internal cues, we temporarily inactivated these individual nuclei in two monkeys trained to make visually triggered (VT) and internally generated (IG) limb movements. Infusions of lignocaine centered within VPLo caused hemiplegia during which movements of the contralateral arm rarely were performed in either task for a short period of time ( approximately 5-30 min). When VT responses were produced, they had prolonged reaction times and movement times and a higher incidence of trajectory abnormalities compared with responses produced during the preinfusion baseline period. In contrast, those IG responses that were produced remained relatively normal. Infusions centered within area X never caused hemiplegia. The only deficits observed were an increase in reaction time and movement amplitude variability and a higher incidence of trajectory abnormalities during VT trials. Every other aspect of both the VT and IG movements remained unchanged. Infusions centered within VLo reduced the number of movements attempted during each block of trials. This did not appear to be due to hemiplegia, however, as voluntary movements easily could be elicited outside of the trained tasks. The other main deficit resulting from inactivation of VLo was an increased reaction time in the VT task. Finally, infusions centered within VApc caused IG movements to become slower and smaller in amplitude, whereas VT movements remained unchanged. Control infusions with saline did not cause any consistent deficits. This pattern of results implies that VPLo and VLo play a role in the production of movements in general regardless of the context under which they are performed. They also suggest that VPLo contributes more specifically to the execution of movements that are visually triggered and guided, whereas area X contributes specifically to the initiation of such movements. In contrast, VApc appears to play a role in the execution of movements based on internal cues. These results are consistent with the hypothesis that specific subcircuits within the cerebello- and basal ganglio-thalamo-cortical systems preferentially contribute to movements based on external versus internal cues.

Analysis of Variance↗

Frequency analysis of involuntary movements during wrist tracking: a way to identify ms patients with tremor who benefit from thalamotomy.

To identify those multiple sclerosis (MS) patients with disabling tremor who will benefit most from thalamotomy, measurements of frequency spectra of involuntary movements during visually guided wrist tracking were carried out in 11 consecutive patients with MS before and after ventrolateral thalamotomy. Thalamotomy was significantly more effective if patients had disruptive action tremor which appeared as a single peak in the frequency spectra. Such patients showed an average reduction of nearly 80% in tremor magnitude after thalamotomy. In comparison, surgery produced an average reduction of only 30% in 3 other patients who had action tremor but showed multiple peaks in the frequency spectra. Frequency analysis of involuntary movements identifies those MS patients with disabling tremor who benefited most from thalamotomy.

Adult↗

Local muscular fatigue and attentional processes in a fencing task.

Study of the effects of brief exercise on mental processes by Tomporowski and Ellis (1986) has shown that moderate muscular tension improves cognitive performance while low or high tension does not. Improvements in performance induced by exercise are commonly associated with increase in arousal, while impairments are generally attributed to the effects of muscular or central fatigue. To test two hypotheses, that (1) submaximal muscular exercise would decrease premotor time and increase would increase the attentional and preparatory effects observed in premotor time 9 men, aged 20 to 30 years, performed an isometric test at 50% of their maximum voluntary contraction between blocks of a 3-choice reaction-time fencing task. Analysis showed (1) physical exercise did not improve postexercise premotor time, (2) muscular fatigue induced by isometric contractions did not increase motor time, (3) there was no effect of exercise on attentional and preparatory processes involved in the postexercise choice-RT task. The invalidation of hypotheses was mainly explained by disparity in directional effects across subjects and by use of an exercise that was not really fatiguing.

Adult↗

Changes in motion perception following oculomotor smooth pursuit adaptation.

The hypothesis that oculomotor smooth pursuit (SP) adaptation is accompanied by alterations in velocity perception was tested by assessing coherence thresholds, using random-dot kinematograms before and after the adaptation paradigm. The results showed that the sensitivity to coherent motion at 10 deg/sec (the initial target velocity during adaptation) was reduced after the SP adaptation, ending up at a level that was between those normally observed for velocities of 10 and 20 deg/sec. This is consistent with an overestimation of the velocity of the coherent motion and suggests that SP adaptation alters not only the oculomotor output, but also the perception of target velocity.

Acceleration↗

Can sensitivity to auditory frequency modulation predict children's phonological and reading skills?

Understanding how letter units represent particular speech sounds is a crucial skill for developing competent reading skills. However it is not known whether such phonological ability is constrained by basic auditory capacities such as those necessary for detecting the frequency modulations characteristic of many phonemes. Here we show that nearly 40% of the variability in normal children's phonological and reading skills can be predicted from their sensitivity to 2 Hz frequency modulated (FM) tones. This relationship does not hold for sensitivity to 240 Hz FM. Because lower but not higher rates of FM provide information important for speech comprehension, dynamic auditory sensitivity is likely to play an important role in children's phonological and reading skill development.

Acoustic Stimulation↗

A genome-wide search strategy for identifying quantitative trait loci involved in reading and spelling disability (developmental dyslexia).

Family and twin studies of developmental dyslexia have consistently shown that there is a significant heritable component for this disorder. However, any genetic basis for the trait is likely to be complex, involving reduced penetrance, phenocopy, heterogeneity and oligogenic inheritance. This complexity results in reduced power for traditional parametric linkage analysis, where specification of the correct genetic model is important. One strategy is to focus on large multigenerational pedigrees with severe phenotypes and/or apparent simple Mendelian inheritance, as has been successfully demonstrated for speech and language impairment. This approach is limited by the scarcity of such families. An alternative which has recently become feasible due to the development of high-throughput genotyping techniques is the analysis of large numbers of sib-pairs using allele-sharing methodology. This paper outlines our strategy for conducting a systematic genome-wide search for genes involved in dyslexia in a large number of affected sib-pair familites from the UK. We use a series of psychometric tests to obtain different quantitative measures of reading deficit, which should correlate with different components of the dyslexia phenotype, such as phonological awareness and orthographic coding ability. This enable us to use QTL (quantitative trait locus) mapping as a powerful tool for localising genes which may contribute to reading and spelling disability.

Alleles↗

Effects of visual feedback on manual tracking and action tremor in Parkinson's disease.

Visual feedback is one of the key elements in on-line control of smooth manual tracking. To in- vestigate the effects basal ganglia dysfunction have on visual feedback control, we have tested six advanced Parkinson's disease (PD) patients in comparison with normal controls using visually guided wrist tracking tasks. Tracking performance was assessed under three visual conditions: (1) both guiding target and movement cursor were displayed continuously; (2) the target display was turned off for the second half of each trial; or (3) the cursor display, but not the target, was turned off for the second half of each trial. Thus, for the second half of each trial under conditions 2 and 3, no visual feedback of the relationship between the target and the cursor was available. Results showed that although PD patients had significantly larger tracking errors than controls, and errors significantly increased in both PD patients and controls after withdrawing either visual cue, increases in tracking errors in PD were not significantly different from those in controls. Nor were any significant changes found in the frequency (6-8 Hz) or magnitude of the PD patient's action tremor after withdrawing visual feedback. These results suggest that on-line movement control of wrist tracking movements in advanced PD is not especially reliant on visual feedback. In conjunction with our previous study of multiple sclerosis (MS) patients, the present results confirm that the basal ganglia is less involved in visual guidance of smooth manual tracking than the cerebellar circuits.

Aged↗

The role of the pedunculopontine region in basal-ganglia mechanisms of akinesia.

The akinesia of Parkinsonism is relieved by pallidotomy and subthalamic nucleotomy, but not by thalamotomy. Therefore, this disabling symptom probably depends upon connections other than the pallidalthalamocortical tracts, possibly efferents of the medial pallidum descending to the upper brainstem. We have previously demonstrated akinesia in the normal monkey following radiofrequency lesioning in the region of the pedunculopontine nucleus (PPN), one of the primary targets for descending pallidal outflow. Here, we confirm that selectively destroying neurones in the PPN area, whilst sparing fibres of passage, results in an akinetic state in normal macaques.

Alfaxalone Alfadolone Mixture↗

Psychophysical sensitivity and physiological response to amplitude modulation in adult dyslexic listeners.

This study reports two experiments conducted to assess the sensitivity of dyslexic listeners to amplitude modulation (AM) of acoustic stimuli. The smallest detectable depth of AM of white noise was measured as a function of modulation frequency. Dyslexic listeners had significantly higher thresholds of AM depth than did matched control listeners. We also recorded the scalp potential evoked by AM of white noise (the amplitude modulation following response, AMFR). Dyslexic listeners had significantly smaller AMFRs than did matched control listeners. The reduced AMFR is consistent with reduced sensitivity to AM, and there was a strong association between these psychophysical and physiological measures. This deficit in AM sensitivity may result in impaired perception of the AM present in speech.

Adult↗

A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia.

Recent application of nonparametric-linkage analysis to reading disability has implicated a putative quantitative-trait locus (QTL) on the short arm of chromosome 6. In the present study, we use QTL methods to evaluate linkage to the 6p25-21.3 region in a sample of 181 sib pairs from 82 nuclear families that were selected on the basis of a dyslexic proband. We have assessed linkage directly for several quantitative measures that should correlate with different components of the phenotype, rather than using a single composite measure or employing categorical definitions of subtypes. Our measures include the traditional IQ/reading discrepancy score, as well as tests of word recognition, irregular-word reading, and nonword reading. Pointwise analysis by means of sib-pair trait differences suggests the presence, in 6p21.3, of a QTL influencing multiple components of dyslexia, in particular the reading of irregular words (P=.0016) and nonwords (P=.0024). A complementary statistical approach involving estimation of variance components supports these findings (irregular words, P=.007; nonwords, P=.0004). Multipoint analyses place the QTL within the D6S422-D6S291 interval, with a peak around markers D6S276 and D6S105 consistently identified by approaches based on trait differences (irregular words, P=.00035; nonwords, P=.0035) and variance components (irregular words, P=.007; nonwords, P=.0038). Our findings indicate that the QTL affects both phonological and orthographic skills and is not specific to phoneme awareness, as has been previously suggested. Further studies will be necessary to obtain a more precise localization of this QTL, which may lead to the isolation of one of the genes involved in developmental dyslexia.

Adolescent↗

Distal versus proximal arm tremor in multiple sclerosis assessed by visually guided tracking tasks.

OBJECTIVES: To compare action tremor (AT) during manual tracking in normal subjects and patients with multiple sclerosis with tremor (MS-tremor group) and without tremor (MS-no tremor group), and to differentiate tremor occurring predominantly around the distal joint from that involving the proximal joints of the arm. METHODS: Subjects performed both a visually guided ramp tracking task using wrist flexion/extension and a whole arm circle tracking task using shoulder movement. Action tremor at the wrist or shoulder was computed as the SD of the tracking velocity. The ratio of wrist:arm tremor was then calculated to differentiate distal from proximal tremor in the tested arm. Frequency spectra of the records were also examined. RESULTS: During wrist tracking, AT in patients with multiple sclerosis contained a major frequency component at 4-5 Hz; the frequency was slightly lower during whole arm tracking. The ratio of wrist:arm tremor was significantly higher in the MS-tremor group. Of 12 tested arms, eight had tremor significantly weighted towards the distal joint, only one towards the proximal joint, and three had a ratio inside the control range. CONCLUSIONS: AT in the arms of patients with multiple sclerosis can be effectively differentiated into proximal or distal using these two different tracking tasks. Despite the variability of the effects of multiple sclerosis, most of the AT was distal rather than proximal in this group of patients. Possibly conduction block along the corticocerebellocortical pathways caused this distal tremor.

Adult↗