Biomedical subjects

J F Stein

Publications and source records attributed to J F Stein.

At least 19 recordsLinked to original sources

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

Sensitivity to dynamic auditory and visual stimuli predicts nonword reading ability in both dyslexic and normal readers.

BACKGROUND: Developmental dyslexia is a specific disorder of reading and spelling that affects 3-9% of school-age children and adults. Contrary to the view that it results solely from deficits in processes specific to linguistic analysis, current research has shown that deficits in more basic auditory or visual skills may contribute to the reading difficulties of dyslexic individuals. These might also have a crucial role in the development of normal reading skills. Evidence for visual deficits in dyslexia is usually found only with dynamic and not static stimuli, implicating the magnocellular pathway or dorsal visual stream as the cellular locus responsible. Studies of such a dissociation between the processing of dynamic and static auditory stimuli have not been reported previously. RESULTS: We show that dyslexic individuals are less sensitive both to particular rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to dynamic visual-motion stimuli. There were high correlations, for both dyslexic and normal readers, between their sensitivity to the dynamic auditory and visual stimuli. Nonword reading, a measure of phonological awareness believed crucial to reading development, was also found to be related to these sensory measures. CONCLUSIONS: These results further implicate neuronal mechanisms that are specialised for detecting stimulus timing and change as being dysfunctional in many dyslexic individuals. The dissociation observed in the performance of dyslexic individuals on different auditory tasks suggests a sub-modality division similar to that already described in the visual system. These dynamic tests may provide a non-linguistic means of identifying children at risk of reading failure.

Acoustic Stimulation↗

PubMed1998

Metabolic abnormalities in developmental dyslexia detected by 1H magnetic resonance spectroscopy.

BACKGROUND: Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. METHODS: We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. FINDINGS: We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. INTERPRETATION: We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.

Adult↗

PubMed1998

Microstimulation of movements from cerebellar-receiving, but not pallidal-receiving areas of the macaque thalamus under ketamine anaesthesia.

The motor thalamic areas receiving input from the globus pallidus (VA) and the cerebellar nuclei (VL) appear to have different roles in the generation and guidance of movements. In order to further test these differences, we used electrical stimulation to map the ventro-anterior and ventro-lateral nuclei of the thalamus in three ketamine anaesthetised monkeys. Movements were readily evoked from VL at currents of down to 10 microA. The movements were typically multijoint, and stimulation could evoke arm and trunk or arm and facial movement at the same current threshold. Evoked arm movements often involved multiple joints, with or without finger movements. Facial movements included the lips, tongue, jaw, eyebrows and, occasionally, the eyes. The thalamic map was topographic, but complex with at least two separate regions related to arm movement. Very few sites within the VA could stimulate movement, even at high currents. We therefore suggest that the cerebellar projections to motor regions of the cortex, which pass through the VL thalamic nuclei, have a different relationship and are closer to movement execution than the projections from basal ganglia via the ventro-anterior nucleus.

Anesthetics, Dissociative↗

PubMed1998

Peak power and pulmonary oxygen uptake during knee extension exercise--comparisons among different incremental protocols.

Four incremental protocols of knee extension exercise of different stage durations were compared to study the effect of the protocol upon power output at the last stage (Ppeak). Previous studies of knee extension have found very different power outputs with similar ergometers and these large differences have been interpreted as being the result of the fatigue due to the durations of the protocols. The knee extension device used in previous studies was modified to avoid the action of the knee and hip flexors: the subjects pushing on a lever instead of pulling a rod. In the present study five subjects performed four incremental knee extension exercises which differed with regard to stage duration (60, 90, 180 or 360 s) on this ergometer. The Ppeak, peak oxygen uptake (VO2peak) and peak heart rate (HRpeak) were measured at the end of each of these four incremental protocols. In eight subjects, the reliability of the protocols with the two shortest increments (60 and 90-s stages) was verified by measuring Ppeak at 60 s and 90 s (Ppeak60, Ppeak90) twice. The knee ergometer proposed in the present paper was easy to use without any special training and should improve the measurement of Ppeak. The Ppeak60 [49.4 (SD 5.6) W] was higher than at 180 s [Ppeak180), 43.6 (SD 5.8) W, P < 0.05] and at 360 s [Ppeak360, 43.4 (SD 5.3) W, P < 0.05]. All the other differences in Ppeak, VO2 peak and HRpeak were not significant. All correlations between Ppeak60, Ppeak90, Ppeak180 and Ppeak360 were significant, except those between Ppeak360 and Ppeak90 or Ppeak180. The effect of the stage duration on power output and oxygen uptake at the end of the knee extension exercises was not great. Consequently, the large differences in power output and oxygen uptake observed in previous studies cannot be explained by the protocol only. The significant difference between Ppeak 60 and Ppeak90 was of the order of 10% in agreement with findings in the literature using cycle ergometry. The reliability of Ppeak60 and Ppeak90 was high and the use of these protocols can be recommended if further studies show that the measurement of Ppeak, is useful in the evaluation of local endurance.

Adult↗

PubMed1998

Magnocellular visual function and children's single word reading.

Recent research has shown that reading disabled children find it unusually difficult to detect flickering or moving visual stimuli, consistent with impaired processing in the magnocellular visual stream. Yet, it remains controversial to suggest that reduced visual sensitivity of this kind might affect children's reading. Here we suggest that when children read, impaired magnocellular function may degrade information about where letters are positioned with respect to each other, leading to reading errors which contain sounds not represented in the printed word. We call these orthographically inconsistent nonsense errors "letter" errors. To test this idea we assessed magnocellular function in a sample of 58 unselected children by using a coherent motion detection task. We then gave these children a single word reading task and found that their "letter" errors were best explained by independent contributions from motion detection (i.e., magnocellular function) and phonological awareness (assessed by a spoonerism task). This result held even when chronological age, reading ability, and IQ were controlled for. These findings suggest that impaired magnocellular visual function, as well as phonological deficits may affect how children read.

Child↗

PubMed1997

Analysis of action tremor and impaired control of movement velocity in multiple sclerosis during visually guided wrist-tracking tasks.

We investigated the relationship between action tremor (AT) and impaired control of movement velocity (MV) in visually guided tracking tasks, in normal subjects and in patients with multiple sclerosis (MS) with or without motor deficits. The effects of withdrawing visual feedback of either the target or the cursor were then investigated. Visually cued simple reaction times (SRTs) were also measured. The effects of thalamotomy on motor performance in these tasks were evaluated in seven patients. In the MS patients with tremor, there was no correlation between AT and impairment in control of MV, but the latter was highly correlated with an increased delay in SRT. Withdrawal of visually guiding cues increased the error significantly in MV, but reduced AT by approximately 30% in magnitude. Frequency analysis indicated that the AT had two components: (a) non-visual-dependent, oscillatory movements, mainly at 4 Hz; and (2) visual-dependent, repetitive movements, with significant power at 1-2 Hz. Thalamotomy significantly reduced AT but hardly improved accuracy in MV. These results suggest that visual feedback of a spatial mismatch signal may provoke a visually dependent repetitive movement contributing to AT. Conduction delays along either the cortico-cerebello-cortical or the proprioceptive pathways and impaired working memory caused by MS may be responsible for the movement disorders in these patients.

Adult↗

PubMed1997

Effect of time and frequency manipulation on syllable perception in developmental dyslexics.

Many people with developmental dyslexia have difficulty perceiving stop consonant contrasts as effectively as other people and it has been suggested that this may be due to perceptual limitations of a temporal nature. Accordingly, we predicted that perception of such stimuli by listeners with dyslexia might be improved by stretching them in time-equivalent to speaking slowly. Conversely, their perception of the same stimuli ought to be made even worse by compressing them in time-equivalent to speaking quickly. We tested 15 children with dyslexia on their ability to identify correctly consonant-vowel-consonant (CVC) stimuli that had been stretched or compressed in the time domain. We also tested their perception of the same CVC stimuli after the formant transitions had been stretched or compressed in the frequency domain. Contrary to our predictions, we failed to find any systematic improvement in their performance with either manipulation. We conclude that simple manipulations in the time and frequency domains are unlikely to benefit the ability of people with dyslexia to discriminate between CVCs containing stop consonants.

Adolescent↗

PubMed1997

Scalp potentials evoked by amplitude-modulated tones in dyslexia.

We recorded the far-field EEG potential evoked by amplitude modulation of acoustic stimuli (the amplitude modulation following response, AMFR) in adults with developmental dyslexia and in a matched control group of adults with no history of reading problems. The mean AMFR recorded from participants with dyslexia was significantly smaller than that recorded from members of the control group. In contrast, the amplitude of the click-evoked auditory brainstem response (ABR) was not significantly different between participant groups. Also, there was no difference between participant groups in the latency of the AMFR or ABR. The reduced AMFR in listeners with dyslexia may reflect impaired ability of the auditory system to follow rapid changes in stimulus energy, a cue believed to be important in the perception of speech.

Adult↗

PubMed1996

Auditory temporal coding in dyslexia.

Developmental dyslexia is generally believed to result from impaired linguistic processing rather than from deficits in low-level sensory function. Challenging this view, we studied the perception of non-verbal acoustic stimuli and low-level auditory evoked potentials in dyslexic adults. Compared with matched controls, dyslexics were selectively impaired in tasks (frequency discrimination and binaural unmasking) which rely on decoding neural discharges phase-locked to the fine structure of the stimulus. Furthermore, this ability to use phase-locking was related to reading ability. In addition, the evoked potential reflecting phase-locked discharges was significantly smaller in dyslexics. These results demonstrate a low-level auditory impairment in dyslexia traceable to the brainstem nuclei.

Adult↗

PubMed1996

Squints and diplopia seen after brain damage.

The aim of this study was to investigate the incidence of squint after brain damage. We performed an observational study on 239 consecutive patients admitted to a specialist neurological rehabilitation unit: 129 with stroke, 84 with head injury and 26 with other conditions. Standard orthoptic measures, including visual acuity, cover test, eye movement recording and tests of binocular function were performed. Of all the patients, 89 (37%), were found to have squints, but only 32 of these (36%) experienced double vision. Brain stem lesions causing peripheral ocular motor impairment were found in a high proportion of patients after head injury (56%). Squints were found in 27 of 95 (28%) patients with cortical strokes, many with no other signs of brain stem involvement. Left was just as likely as right hemisphere damage to be associated with squint, but right-sided lesions seemed to protect against diplopia. We conclude that squint is common after brain damage, even if the brain stem is not obviously affected, but only a minority of these patients with acquired squint suffer diplopia.

Brain Damage, Chronic↗

PubMed1996

Analysis of perceptual confusions between nine sets of consonant-vowel sounds in normal and dyslexic adults.

It is widely accepted that most developmental dyslexics perform poorly on tasks which assess phonological awareness. One reason for this association might be that the early or "input" phonological representations of speech sounds are distorted or noisy in some way. We have attempted to test this hypothesis directly. In Experiment 1, we measured the confusions that adult dyslexics and controls made when they listened to nine randomly presented consonant-vowel (CV) segments [sequence: see text] under four conditions of increasing white noise masking. Subjects could replay stimuli and were under no obligation to respond quickly. Responses were selected with a computer mouse from a set of nine letter-strings, corresponding to the auditory stimuli, presented on a VDU. While the overall pattern of confusions made by dyslexics and controls was very similar for this stimulus set, dyslexics confused [sequence: see text] significantly more than did controls. In Experiment 2, subjects heard each stimulus once only and were forced to respond as quickly as possible. Under these timed conditions, the pattern of confusions made by dyslexics and controls was the same as before, but dyslexics took longer to respond than controls. The slower responses of dyslexics in Experiment 2 could have arisen because: (a) they were slower at processing the auditory stimuli than controls, (b) they had worse visual pattern memory for letter strings than controls, (c) they were slower than controls at using the computer mouse. In Experiments 3, 4 and 5 subjects carried out control tasks which eliminated each of these possibilities and confirmed that the results from the auditory tasks genuinely reflected subjects' speech perception. We propose that the fine structure of dyslexics' input phonological representations should be further explored with this confusion paradigm by using other speech sounds containing VCs, CCVs and VCCs.

Adult↗

PubMed1996

Differences in visuospatial judgement in reading-disabled and normal children.

Both visual and verbal impairments have been reported in two independent streams of research into the etiology of dyslexia or reading-disability. To address the question of the presence of either abnormality in reading-disabled children, visuospatial and phonological ability were assessed and contrasted in 39 Normal and 26 Reading-disabled children. To assess whether these deficits are unique to dyslexia, scores were also compared to those of a group of 12 Poor Readers ("garden-variety" backward readers with low IQs). The Benton Judgement of Line Orientation Test was used for its simplicity and clinical reliability: Reading-disabled subjects performed significantly worse than Normal readers (but similar to Poor Readers). Reading-disabled subjects performed worse for lines in the left-hemifield compared to Normal subjects and also had a greater tendency to scan the task in reverse order (left-to-right) from the usual right-to-left scanning pattern observed in the Normal group when performing this test. When both verbal and visuospatial variables were combined in a multiple regression analysis, 71% of reading variance could be accounted for. These results suggest that Reading-disabled children not only have poor phonological awareness, but they also show visuospatial deficits. However, poor performance on both these tasks was also observed in the group of Poor Readers, suggesting that these deficits are not unique to children with specific reading disability. The results lend further evidence to the hypothesis that reading disability cannot solely be attributed to left-hemisphere dysfunction resulting in phonological impairment. There are other behavioral deficits, possibly caused by a common mechanism, some of which, like visuospatial ability, can be measured by simple behavioral tests such as the Judgment of Line Orientation Test.

Child↗

PubMed1996

Activity of interpositus neurons during a visually guided reach.

Neurons in the cerebellar interpositus nucleus greatly increase their discharge rates when a monkey reaches out to grasp an object. However, when the monkey is required to track a target on a screen by moving a manipulandum, the increase in discharge rate is relatively small or nonexistent. Moving the hand directly to a target is a visuomotor task that may be fundamentally different from a remote tracking task. We hypothesize that the interpositus nucleus is specialized for direct visual guidance of the limb or, alternatively, interpositus is specialized for controlling hand movements required to grasp an object. A monkey was trained to hold a sensor and move it directly over a visual target to obtain water reward. Small drawers were mounted next to two of the targets; on some trials a drawer would open so that the monkey would reach out and retrieve a raisin that had been placed in it. Interpositus neurons discharged strongly during reach to grasp the raisin but not when the monkey was positioning the sensor over the target. For individual cells, discharge pattern and amplitude were largely independent of the size and direction of the reach to grasp, suggesting that interpositus does not control direction or amplitude of the reach. The results are consistent with the hypothesis that neurons in forelimb regions of interpositus participate in the control of hand movements used in grasping, but they are not consistent with the hypothesis that interpositus neurons participate in direct visual guidance of the limb.

Animals↗

PubMed1995

Temporal and spatial processing in reading disabled and normal children.

The ability to process temporal and spatial visual stimuli was studied to investigate the role these functions play in the reading process. Previous studies of this type have often been confounded by memory involvement, or did not take into account the evidence which suggests a visual transient deficient in some dyslexics. Normal (n = 39), reading disabled (n = 26), and backward reading children (n=12) were compared on a visual computer game, which consisted of a temporal and a analogous spatial dot counting task. Reading disabled children performed significantly worse than normal children on the Temporal Dot Task, but were only mildly impaired on the Spatial Dot Task, Backward readers were not significantly better than the reading disabled group on either task, suggesting that poor poor visual temporal processing is not specific to dyslexia. In a group of 93 children, a regression model including age, verbal IQ, phonological awareness, and visual temporal processing ability, predicted 73% of the variance of reading ability. The results suggest that dyslexics perform worse in tasks that require fast, sequential processing and that this impairment may be partially responsible for their reading difficulties.

Attention↗

PubMed1995

Verbal and visual problems in reading disability.

Most individuals interested in reading disability favor the view that disordered language processing is the main cause of children's reading problems and that visual problems are seldom, if ever, responsible. Nevertheless, in a preliminary study (Eden, Stein, & Wood, 1993) we showed that visuospatial and oculomotor tests can be used to differentiate children with reading disabilities from nondisabled children. In the present study we investigated a larger sample of children to see if these findings held true. Using 93 children from the Bowman Gray Learning Disability Project (mean age = 11.3 years; 54 boys, 39 girls), we compared the phonological and visuospatial abilities of nondisabled children (children whose reading at fifth grade rated a Woodcock-Johnson reading standardized score between 85 and 115), and children with reading disability (whose reading standardized score was below 85 on the Woodcock-Johnson). In addition to performing poorly on verbal tests, the children with reading disability were significantly worse than nondisabled children at many visual and eye-movement tasks. A high proportion of the variance (68%) in reading ability of both the nondisabled children and those with reading disability could be predicted by combining visual and phonological scores in a multiple regression. These results provide further support for the hypothesis that reading disability may, to some extent, result from dysfunction of the visual and oculomotor systems.

Brain↗

PubMed1994

Differences in eye movements and reading problems in dyslexic and normal children.

It has been suggested that eye movement abnormalities seen in dyslexics are attributable to their language problems. In order to investigate this claim, we studied eye movements in dyslexic children, during several non-reading tasks. Dyslexic children were compared to normal and backward readers on measures of fixation, vergence amplitude, saccade and smooth pursuit. The results were compared to the children's phonological ability. Dyslexic children (n = 26) had significantly worse eye movement stability during fixation of small targets than normal children (n = 39). Vergence amplitudes were lower for dyslexics than for controls. A qualitative assessment of saccadic eye movements revealed that dyslexics exhibit fixation instability at the end of saccades. Assessment of smooth pursuit revealed poor smooth pursuit in the dyslexic group, particularly when pursuing a target moving from left to right. Dyslexic children also performed significantly worse than normal children on a test of phonological awareness (Pig Latin). Eye movement results were studied in the light of the findings on phonological awareness: dyslexics with small vergence amplitudes also always have poor phonemic awareness. However, poor fixation control is found in dyslexics with or without poor phonological ability. The backward reading children performed similar to the dyslexics on all tests, suggesting that the deficiencies observed in this study are not specific to children with dyslexia. The problems experienced by the children (revealed by a questionnaire) are in agreement with those measured in terms of eye movement recordings and phonemic awareness. Sex, handedness, IQ or the presence of attention deficit disorder (ADD) did not appear to influence the children's performances on any of the eye movement tasks. The presence of oculomotor abnormalities in a non-reading task strongly suggests that the underlying deficit in the control of eye movements seen in dyslexics is not caused by language problems alone.

Attention Deficit Disorder with Hyperactivity↗