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Biomedical subjects

J F Stein

Publications and source records attributed to J F Stein.

At least 19 recordsLinked to original sources
PubMed2006

Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia.

The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.

5' Untranslated Regions↗
PubMed2005

Yellow filters can improve magnocellular function: motion sensitivity, convergence, accommodation, and reading.

The magnocellular system plays an important role in visual motion processing, controlling vergence eye movements, and in reading. Yellow filters may boost magnocellular activity by eliminating inhibitory blue input to this pathway. It was found that wearing yellow filters increased motion sensitivity, convergence, and accommodation in many children with reading difficulties, both immediately and after three months using the filters. Motion sensitivity was not increased using control neutral density filters. Moreover, reading-impaired children showed significant gains in reading ability after three months wearing the filters compared with those who had used a placebo. It was concluded that yellow filters can improve magnocellular function permanently. Hence, they should be considered as an alternative to corrective lenses, prisms, or exercises for treating poor convergence and accommodation, and also as an aid for children with reading problems.

Accommodation, Ocular↗
PubMed2005

Midbrain ataxia.

Explore the source record for details and available documents.

Brain Diseases↗
PubMed2003

Why did language develop?

Language developed for communication, to facilitate learning the use of tools and weapons, to plan hunting and defence, to develop a "theory of mind" and the tools of thought, and to attract and keep a mate. The adaptations required took place over many millions of years. The first important one was left-sided specialisation of the neural apparatus controlling involuntary emotional vocalisations that began more than 200 million years ago. The next was the development in primates of "mirror neurones" in the pre-motor cortex some 45 million years ago. These enabled the imitation and voluntary control of previously involuntary manual gestures and vocalisations. The third important adaptation was the descent of the larynx, 100,000 years ago, which greatly increased the phonological range of vocalisations that could be made. Thus, language did not develop all at once as suggested by Chomsky, but evolved gradually building upon adaptations originally meeting quite different needs.

Brain↗
PubMed2003

Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.

Adult↗
PubMed2002

The oscillatory activity in the Parkinsonian subthalamic nucleus investigated using the macro-electrodes for deep brain stimulation.

OBJECTIVES: To investigate the oscillatory activity in the Parkinsonian subthalamic nucleus using the macro-electrodes for deep brain stimulation. METHODS: During bilateral deep brain stimulating electrode implantation, spontaneous and evoked field potentials were recorded from the subthalamic nucleus (STN) in two patients with Parkinson's disease (PD) during spontaneous resting tremor, passive manipulation of the wrist, and following electrical stimulation of the contralateral STN. RESULTS: Frequency analysis of the STN field potentials recorded during spontaneous resting tremor showed significant coherence with electromyographic activity in the contralateral arm, suggesting a close involvement of the STN in the generation of resting tremor in PD. The STN responded to passive movement of the contralateral wrist, but not to ipsilateral movement. High frequency (100 Hz) electrical stimulation of the STN induced tremor (4 Hz) in both forearms, and also oscillation of the contralateral STN (4 Hz). In contrast, low frequency (5 Hz) stimulation induced contralateral arrhythmic involuntary movement (3 Hz), but without altering the contralateral STN activity. CONCLUSIONS: We propose that the functional connection between the STN and arm muscles is mainly contralateral, but cross talk may occur between bilateral STN via a frequency-dependent pathway.

Animals↗
PubMed2002

Exploration of the role of the upper brainstem in motor control.

The rostral areas of the brainstem have been extensively studied in higher mammals and to a lesser extent in humans in the last two decades, looking for anatomical, electrophysiological and neurochemical evidence of involvement in the initiation and control of voluntary movement. This has come with the realisation that the axial symptoms of advanced Parkinson's disease (PD), like akinesia, postural impairment and gait freezing, are relatively less responsive to current medical and surgical treatments directed primarily at the basal ganglia and thalamus. The pedunculopontine nucleus (PPN) is one such area of interest. We have found that lesioning and electrical stimulation at high frequencies of the PPN region in the normal behaving primate induces akinesia, and low frequency stimulation can induce tremor. Micro-injections of gamma-aminobutyric acid (GABA) receptor A agonist, muscimol, into the PPN decreases activity. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated Parkinsonian primate model, bicuculline, a GABA(A) antagonist, can alleviate akinesia when infused into the PPN region. This may suggest new targets for treating the intractable akinetic symptoms of advanced PD.

Animals↗
PubMed2002

Auditory frequency discrimination in adult developmental dyslexics.

Developmental dyslexics reportedly discriminate auditory frequency poorly. A recent study found no such deficit. Unlike its predecessors, however, it employed multiple exposures per trial to the standard stimulus. To investigate whether this affects frequency discrimination in dyslexics, a traditional two-interval same-different paradigm (2I_1A_X) and a variant with six A-stimuli per trial (2I_6A_X) were used here. Frequency varied around 500 Hz; interstimulus interval (ISI) ranged between 0 and 1,000 msec. Under 2I_1A_X, dyslexics always had larger just noticeable differences (JNDs) than did controls. Dyslexic and control JNDs were equal at shorter ISIs under 2I_6A_X, but dyslexics became worse than controls at longer ISIs. Signal detection analysis suggests that both sensory variance and trace variance are larger in dyslexics than in controls.

Adult↗
PubMed2001

Motor cortex stimulation for neuropathic pain.

Motor cortex stimulation is increasingly reported in the literature as a surgical option for the alleviation of neuropathic pain. The authors review the published literature and present their results including those demonstrated in a randomized controlled trial that confirmed the efficacy of the procedure. Patient selection and prediction of outcomes, however, remain difficult issues.

Adult↗
PubMed2001

Are dyslexics' visual deficits limited to measures of dorsal stream function?

We tested the hypothesis that the differences in performance between developmental dyslexics and controls on visual tasks are specific for the detection of dynamic stimuli. We found that dyslexics were less sensitive than controls to coherent motion in dynamic random dot displays. However, their sensitivity to control measures of static visual form coherence was not significantly different from that of controls. This dissociation of dyslexics' performance on measures that are suggested to tap the sensitivity of different extrastriate visual areas provides evidence for an impairment specific to the detection of dynamic properties of global stimuli, perhaps resulting from selective deficits in dorsal stream functions.

Adult↗
PubMed2001

Increased response to visual feedback of drug-induced dyskinetic movements in advanced Parkinson's disease.

To investigate the response to visual feedback of involuntary movements which have a frequency composition similar to cerebellar tremor but are not caused by cerebellar damage, we have tested six advanced Parkinson's disease (PD) patients with drug-induced dyskinetic movements 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. The response to visual feedback of drug-induced dyskinetic movements at 1-5 Hz in these advanced PD patients were significantly increased than in normal controls. This suggests that increased response to visual feedback might be a common feature of low frequency involuntary movements and not directly caused by cerebellar damages.

Aged↗
PubMed2001

Lateralized cognitive deficits in children following cerebellar lesions.

The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.

Cerebellar Neoplasms↗
PubMed2001

Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK.

We describe a family-based sample of individuals with reading disability collected as part of a quantitative trait loci (QTL) mapping study. Eighty-nine nuclear families (135 independent sib-pairs) were identified through a single proband using a traditional discrepancy score of predicted/actual reading ability and a known family history. Eight correlated psychometric measures were administered to each sibling, including single word reading, spelling, similarities, matrices, spoonerisms, nonword and irregular word reading, and a pseudohomophone test. Summary statistics for each measure showed a reduced mean for the probands compared to the co-sibs, which in turn was lower than that of the population. This partial co-sib regression back to the mean indicates that the measures are influenced by familial factors and therefore, may be suitable for a mapping study. The variance of each of the measures remained largely unaffected, which is reassuring for the application of a QTL approach. Multivariate genetic analysis carried out to explore the relationship between the measures identified a common factor between the reading measures that accounted for 54% of the variance. Finally the familiality estimates (range 0.32-0.73) obtained for the reading measures including the common factor (0.68) supported their heritability. These findings demonstrate the viability of this sample for QTL mapping, and will assist in the interpretation of any subsequent linkage findings in an ongoing genome scan.

Child↗
PubMed2001

Could platelet activating factor play a role in developmental dyslexia?

Post-mortem studies by Galaburda and colleagues on the brains of developmental dyslexics found characteristic neuronal abnormalities: ectopias, microgyria, and fewer large-soma cells in sensory thalamus. An association between dyslexia and immune dysfunction has also been proposed. We describe a mechanism which may explain these observations. Platelet-activating factor (PAF) is a pro-inflammatory lipid implicated in neurological disorders. We propose that PAF may also be involved in dyslexia.

Brain↗
PubMed2001

Stereotactic lesional surgery for the treatment of tremor in multiple sclerosis: a prospective case-controlled study.

The effect of stereotactic lesional surgery for the treatment of tremor in multiple sclerosis was examined in a prospective case-controlled study. Surgery was not undertaken in 33 patients (72% of 46 cases referred for stereotactic surgery), two of whom died within 4 months of referral. Twenty-four multiple sclerosis patients were included in the study; 13 underwent surgery and were matched against 11 controls on the basis of age, sex, expanded disability system scores (EDSS) and disease duration. Assessments were carried out at baseline/preoperatively, and then 3 and 12 months later; these included accelerometric and clinical ratings of tremor, spirography, handwriting, a finger-tapping test, nine-hole peg test, tremor-related disability, general neurological examination, Barthel Activities of Daily Living (ADL) Index of general disability, EDSS, a 0-4 ataxia scale, Mini-Mental State (MMS) examination, speech and swallowing assessments and grip strength. Postoperative MRI scans demonstrated that tremor could be attenuated by lesions centred on the thalamus in seven cases, on the zona incerta in five cases and in the subthalamic nucleus in one case. Two patients developed hemiparesis and in two cases epilepsy recurred. Two surgical patients and one control patient died between the 3 and 6 months assessments. Both groups had a significant deterioration in EDSS but not Barthel ADL Index scores at 1 year, but the difference between the groups was not significant. Similarly, no differences between the groups' rates of deterioration of speech or swallowing or MMS were found. Significant improvements in contralateral upper limb postural (P2) and kinetic tremors, spiral scores and head tremor were detected at 3 and 12 months after surgery (but not handwriting or nine-hole peg test performance). Tremor-related disability and finger-tapping speed were also significantly better 12 months after surgery, the latter having significantly worsened for the control group. A 3 Hz 'filter' for postural (P2) upper limb tremor was detected by accelerometry/spectral analysis above which tremor was always abolished and at or below which some residual tremor invariably remained. Criteria for selecting multiple sclerosis patients for this form of surgery are discussed.

Activities of Daily Living↗
PubMed2001

Targeting the subthalamic nucleus.

The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.

Electric Stimulation Therapy↗