Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

Background

Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a “virtual lesion” in stimulated brain regions, with correspondingly diminished behavioral performance.

Methodology/Principal Findings

Here we investigated the effects of rTMS to visual cortex on subjects'' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task.

Conclusions/Significance

Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.     

Representation of cloned genomic sequences in two sequencing vectors: correlation of DNA sequence and subclone distribution.

Representation of subcloned Caenorhabditis elegans and human DNA sequences in both M13 and pUC sequencing vectors was determined in the context of large scale genomic sequencing. In many cases, regions of subclone under-representation correlated with the occurrence of repeat sequences, and in some cases the under-representation was orientation specific. Factors which affected subclone representation included the nature and complexity of the repeat sequence, as well as the length of the repeat region. In some but not all cases, notable differences between the M13 and pUC subclone distributions existed. However, in all regions lacking one type of subclone (either M13 or pUC), an alternate subclone was identified in at least one orientation. This suggests that complementary use of M13 and pUC subclones would provide the most comprehensive subclone coverage of a given genomic sequence.     

Analysis of a Mutator Activity Necessary for Germline Transposition and Excision of Tc1 Transposable Elements in Caenorhabditis Elegans

The Tc1 transposable element family of the nematode Caenorhabditis elegans consists primarily of 1.6-kb size elements. This uniformity of size is in contrast to P in Drosophila and Ac/Ds in maize. Germline transposition and excision of Tc1 are detectable in the Bergerac (BO) strain, but not in the commonly used Bristol (N2) strain. A previous study suggested that multiple genetic components are responsible for the germline Tc1 activity of the BO strain. To analyze further this mutator activity, we derived hybrid strains between the BO strain and the N2 strain. One of the hybrid strains exhibits a single locus of mutator activity, designated mut-4, which maps to LGI. Two additional mutators, mut-5 II and mut-6 IV, arose spontaneously in mut-4 harboring strains. This spontaneous appearance of mutator activity at new sites suggests that the mutator itself transposes. The single mutator-harboring strains with low Tc1 copy number generated in this study should be useful in investigations of the molecular basis of mutator activity. As a first step toward this goal, we examined the Tc1 elements in these low copy number strains for elements consistently co-segregating with mutator activity. Three possible candidates were identified: none was larger than 1.6 kb.     

A Genetic Mapping System in Caenorhabditis Elegans Based on Polymorphic Sequence-Tagged Sites

We devised an efficient genetic mapping system in the nematode Caenorhabditis elegans which is based upon the differences in number and location of the transposable element Tc1 between the Bristol and Bergerac strains. Using the nearly completed physical map of the C. elegans genome, we selected 40 widely distributed sites which contain a Tc1 element in the Bergerac strain, but not in the Bristol strain. For each site a polymerase chain reaction assay was designed that can distinguish between the Bergerac Tc1-containing site and the Bristol "empty" site. By combining appropriate assays in a single reaction, one can score multiple sites within single worms. This permits a mutation to be rapidly mapped, first to a linkage group and then to a chromosomal subregion, through analysis of only a small number of progeny from a single interstrain cross.     

High-throughput plasmid DNA purification for 3 cents per sample

To accommodate the increasingly rapid rates of DNA sequencing we have developed and implemented an inexpensive, expeditious method for the purification of double-stranded plasmid DNA clones. The robust nature, high throughput, low degree of technical difficulty and extremely low cost have made it the plasmid DNA preparation method of choice in both our expressed sequence tag (EST) and genome sequencing projects. Here we report the details of the method and describe its application in the generation of more than 700 000 ESTs at a rate exceeding 16 000 per week.     

Health professionals and South Africa: supporting change in the health sector.

Now that political change is on the way in South Africa, what should be the position of doctors who are invited to visit the country? Does the "academic boycott" still have relevance? Waterston and Zwi review the case for and against an academic boycott policy, using evidence collected during the recent visit by Physicians for Human Rights (UK) and the Johannes Wier Foundation. The health system in South Africa is still inequitable, and despite progress towards desegregation in hospitals there is little momentum towards universal provision of primary health care, especially in the rapidly growing townships around big cities. The authors consider that pressure on the government should be maintained by outside organisations but that support directed towards appropriate health care should be encouraged, particularly in public health and primary health care.     

The Unc-45 Gene of Caenorhabditis Elegans Is an Essential Muscle-Affecting Gene with Maternal Expression

We have isolated three novel alleles of the unc-45 locus in C. elegans, that are recessive lethals. Two of these alleles, when homozygous, result in a nearly total loss of muscle contraction with a concomitant arrest of development and a displacement of muscle cells. The third allele is similar, but showed maternal rescue by a wild-type allele. All previously identified unc-45 alleles were temperature sensitive and, although they produced paralysis of adult animals, all were homozygous viable. Prior genetic studies with these temperature sensitive alleles had suggested that at least one function of the unc-45 gene product was to interact with the major myosin heavy chain isoform, MHC B, of body wall muscles. Our observations of the lethal alleles suggest that the unc-45 product normally interacts with additional muscle components in both the body wall and pharyngeal muscles. In particular, we suggest that the unc-45 product might interact with all four myosin heavy chains: MHC B; MHC A; and the pharyngeal isoforms, MHC C and MHC D. Maternal rescue of the lethality of the third allele shows that the unc-45 gene product is present in the oocytes, although it may not be necessary until late in development when myofilaments begin to assemble.     

Use of repetitive DNA probes as physical mapping strategy in Caenorhabditis elegans.

A method for linking genomic sequences cloned in yeast artificial chromosomes (YACs) has been tested using Caenorhabditis elegans as a model system. Yeast clones carrying YACs with repeated sequences were selected from a C. elegans genomic library, total DNA was digested with restriction enzymes, transferred to nylon membranes and probed with a variety of repetitive DNA probes. YAC clones that overlap share common bands with one or more repetitive DNA probes. In 159 YAC clones tested with one restriction enzyme and six probes 28 overlapping clones were detected. The advantages and limitations of this method for construction of YAC physical maps is discussed.