Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex affects divided attention immediately after cessation of stimulation

Transcranial magnetic stimulation has evolved into a powerful neuroscientific tool allowing to interfere transiently with specific brain functions. In addition, repetitive TMS (rTMS) has long-term effects (e.g. on mood), probably mediated by neurochemical alterations. While long-term safety of rTMS with regard to cognitive functioning is well established from trials exploring its therapeutic efficacy, little is known on whether rTMS can induce changes in cognitive functioning in a time window ranging from minutes to hours, a time in which neurochemical effects correlated with stimulation have been demonstrated. This study examined effects of rTMS on three measures of executive function in healthy subjects who received one single rTMS session (40 trains of 2 s duration 20 Hz stimuli) at the left dorsolateral prefrontal cortex (DLPFC). Compared to a sham condition one week apart, divided attention performance was significantly impaired about 30-60 min after rTMS, while Stroop-interference and performance in the Wisconsin Card Sorting Test was unaffected after rTMS. Repetitive TMS of the left DLPFC, at stimulation parameters used in therapeutic studies, does not lead to a clinically relevant impairment of executive function after stimulation. However, the significant effect on divided attention suggests that cognitive effects of rTMS are not limited to the of acute stimulation, and may possibly reflect known neurochemical alterations induced by rTMS. Sensitive cognitive measures may be useful to trace those short-term effects of rTMS non-invasively in humans.

Increased genome instability in Escherichia coli lon mutants: relation to emergence of multiple-antibiotic-resistant (Mar) mutants caused by insertion sequence elements and large tandem genomic amplifications

Thirteen spontaneous multiple-antibiotic-resistant (Mar) mutants of Escherichia coli AG100 were isolated on Luria-Bertani (LB) agar in the presence of tetracycline (4 microg/ml). The phenotype was linked to insertion sequence (IS) insertions in marR or acrR or unstable large tandem genomic amplifications which included acrAB and which were bordered by IS3 or IS5 sequences. Five different lon mutations, not related to the Mar phenotype, were also found in 12 of the 13 mutants. Under specific selective conditions, most drug-resistant mutants appearing late on the selective plates evolved from a subpopulation of AG100 with lon mutations. That the lon locus was involved in the evolution to low levels of multidrug resistance was supported by the following findings: (i) AG100 grown in LB broth had an important spontaneous subpopulation (about 3.7x10(-4)) of lon::IS186 mutants, (ii) new lon mutants appeared during the selection on antibiotic-containing agar plates, (iii) lon mutants could slowly grow in the presence of low amounts (about 2x MIC of the wild type) of chloramphenicol or tetracycline, and (iv) a lon mutation conferred a mutator phenotype which increased IS transposition and genome rearrangements. The association between lon mutations and mutations causing the Mar phenotype was dependent on the medium (LB versus MacConkey medium) and the antibiotic used for the selection. A previously reported unstable amplifiable high-level resistance observed after the prolonged growth of Mar mutants in a low concentration of tetracycline or chloramphenicol can be explained by genomic amplification.

Rosette-forming glioneuronal tumor of the fourth ventricle: Report of two cases with a differential diagnostic overview

We report on clinicopathological findings in two cases of rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) occurring in females aged 16 years (Case 1) and 30 years (Case 2). Symptoms included vertigo, nausea, cerebellar ataxia, as well as headaches, and had been present for 4-months and 1 week, respectively. Magnetic resonance imaging (MRI) indicated a cerebellar-based tumor of 1.8cm (Case 1) and 5cm (Case 2) diameter each, bulging into the fourth ventricle. Case 2 involved a cyst-mural-nodule configuration. In both instances, the solid component appeared isointense on T(1) sequences, hyperintense in the T(2) mode, and enhanced moderately. Gross total resection was achieved via suboccipital craniotomy. However, functional recovery was disappointing in Case 1. On microscopy, both tumors comprised an admixture of low-grade astrocytoma interspersed with circular aggregates of synaptophysin-expressing round cells harboring oligodendrocyte-like nuclei. The astrocytic moiety in Case 1 was nondescript, and overtly pilocytic in Case 2. The architecture of neuronal elements variously consisted of neurocytic rosettes, of pseudorosettes centered on a capillary core, as well as of concentric ribbons along irregular lumina. Gangliocytic maturation, especially "floating neurons", or a corresponding immunoreactivity for neurofilament protein was absent. Neither of these populations exhibited atypia, mitotic activity, or a significant labeling for MIB-1. Cerebellar parenchyma included in the surgical specimen did not reveal any preexisting malformative anomaly. Despite sharing some overlapping histologic traits with dysembryoplastic neuroepithelial tumor (DNT), the presentation of RGNT with respect to both patient age and location is consistent enough for this lesion to be singled out as an autonomous entity.