Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings.

Scalp EEG recordings and the classification of interictal epileptiform discharges (IED) in patients with epilepsy provide valuable information about the epileptogenic network, particularly by defining the boundaries of the "irritative zone" (IZ), and hence are helpful during pre-surgical evaluation of patients with severe refractory epilepsies. The current detection and classification of epileptiform signals essentially rely on expert observers. This is a very time-consuming procedure, which also leads to inter-observer variability. Here, we propose a novel approach to automatically classify epileptic activity and show how this method provides critical and reliable information related to the IZ localization beyond the one provided by previous approaches. We applied Wave_clus, an automatic spike sorting algorithm, for the classification of IED visually identified from pre-surgical simultaneous Electroencephalogram-functional Magnetic Resonance Imagining (EEG-fMRI) recordings in 8 patients affected by refractory partial epilepsy candidate for surgery. For each patient, two fMRI analyses were performed: one based on the visual classification and one based on the algorithmic sorting. This novel approach successfully identified a total of 29 IED classes (compared to 26 for visual identification). The general concordance between methods was good, providing a full match of EEG patterns in 2 cases, additional EEG information in 2 other cases and, in general, covering EEG patterns of the same areas as expert classification in 7 of the 8 cases. Most notably, evaluation of the method with EEG-fMRI data analysis showed hemodynamic maps related to the majority of IED classes representing improved performance than the visual IED classification-based analysis (72% versus 50%). Furthermore, the IED-related BOLD changes revealed by using the algorithm were localized within the presumed IZ for a larger number of IED classes (9) in a greater number of patients than the expert classification (7 and 5, respectively). In contrast, in only one case presented the new algorithm resulted in fewer classes and activation areas. We propose that the use of automated spike sorting algorithms to classify IED provides an efficient tool for mapping IED-related fMRI changes and increases the EEG-fMRI clinical value for the pre-surgical assessment of patients with severe epilepsy.

Seed Weight and Trade-Offs: An Experiment in False Rhodes Grasses under Different Aridity Conditions.

The false Rhodes grasses [Leptochloa crinita (Lag.) P.M. Peterson and N.W. Snow and Leptochloa pluriflora (E. Fourn.) P.M. Peterson and N.W. Snow] are considered valuable native forage resources for arid and semiarid rangelands in Argentina and the United States. Effectively using plant materials as forage under aridity conditions requires understanding their resource allocation under those conditions. In the present study, plant functional traits were evaluated in six populations of each false Rhodes grass species from different geographic origin in a humid and an arid region. The evaluation was focused on seed weight, due to the key role of this trait in plant survival. The implication of seed weight in germination under osmotic stress and trade-off relationships between functional traits were also analysed. A fixed ontogenetic variation was found in both species, since populations maintained a stable seed weight across environments. The tolerance to osmotic stress at germination stage was more related to seed weight than to population origin or maternal environment of seeds; heavier-seeded populations produced heavier seedlings instead of a higher number of germinated seeds or higher germination rates. Some traits varied between environments but other traits exhibited a fixed response. Variation patterns among populations were similar within environments and in some cases even for populations from the same geographic origin, revealing a fixed ontogenetic variation; this phenomenon was clearer in L. crinita than in L. pluriflora. Moreover, several different trade-off strategies were detected in both species. These results reinforce the knowledge about the key role of seed weight in survival and performance of seedlings at initial growth stages under arid conditions; however, at advanced stages, other traits would have an important function in growth and development of false Rhodes grasses.

Partial duplication of 18q including a distal critical region for Edwards Syndrome in a patient with normal phenotype and oligoasthenospermia: case report.

Several authors have attempted to construct a phenotype map for duplications of different portions of chromosome 18 to identify a possible critical region (CR) for Edwards Syndrome. Partial duplications of 18q have been reported in the literature involving the distal CR in patients with some clinical features of Edwards Syndrome. Here, we describe a phenotypically normal male with a large duplication on chromosome 18 that involves the proposed distal CR. The lack of clinical features is remarkable, except for pathological semen analysis, which suggests that terminal 17.4 Mb of 18q do not contain the Edwards Syndrome CR. Alternatively, unknown modifier factors or undetected somatic mosaicism might cause incomplete penetrance of this duplication.

Invariant visual representation by single neurons in the human brain.

It takes a fraction of a second to recognize a person or an object even when seen under strikingly different conditions. How such a robust, high-level representation is achieved by neurons in the human brain is still unclear. In monkeys, neurons in the upper stages of the ventral visual pathway respond to complex images such as faces and objects and show some degree of invariance to metric properties such as the stimulus size, position and viewing angle. We have previously shown that neurons in the human medial temporal lobe (MTL) fire selectively to images of faces, animals, objects or scenes. Here we report on a remarkable subset of MTL neurons that are selectively activated by strikingly different pictures of given individuals, landmarks or objects and in some cases even by letter strings with their names. These results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.

Human single-neuron responses at the threshold of conscious recognition.

We studied the responses of single neurons in the human medial temporal lobe while subjects viewed familiar faces, animals, and landmarks. By progressively shortening the duration of stimulus presentation, coupled with backward masking, we show two striking properties of these neurons. (i) Their responses are not statistically different for the 33-ms, 66-ms, and 132-ms stimulus durations, and only for the 264-ms presentations there is a significantly higher firing. (ii) These responses follow conscious perception, as indicated by the subjects' recognition report. Remarkably, when recognized, a single snapshot as brief as 33 ms was sufficient to trigger strong single-unit responses far outlasting stimulus presentation. These results suggest that neurons in the medial temporal lobe can reflect conscious recognition by "all-or-none" responses.

Drivers of seedling establishment success in dryland restoration efforts.

Restoration of degraded drylands is urgently needed to mitigate climate change, reverse desertification and secure livelihoods for the two billion people who live in these areas. Bold global targets have been set for dryland restoration to restore millions of hectares of degraded land. These targets have been questioned as overly ambitious, but without a global evaluation of successes and failures it is impossible to gauge feasibility. Here we examine restoration seeding outcomes across 174 sites on six continents, encompassing 594,065 observations of 671 plant species. Our findings suggest reasons for optimism. Seeding had a positive impact on species presence: in almost a third of all treatments, 100% of species seeded were growing at first monitoring. However, dryland restoration is risky: 17% of projects failed, with no establishment of any seeded species, and consistent declines were found in seeded species as projects matured. Across projects, higher seeding rates and larger seed sizes resulted in a greater probability of recruitment, with further influences on species success including site aridity, taxonomic identity and species life form. Our findings suggest that investigations examining these predictive factors will yield more effective and informed restoration decision-making.

Aridity and grazing as convergent selective forces: an experiment with an Arid Chaco bunchgrass.

It has been proposed that aridity and grazing are convergent selective forces: each one selects for traits conferring resistance to both. However, this conceptual model has not yet been experimentally validated. The aim of this work was to experimentally evaluate the effect of aridity and grazing, as selective forces, on drought and grazing resistance of populations of Trichloris crinita, a native perennial forage grass of the Argentinean Arid Chaco region. We collected seeds in sites with four different combinations of aridity and grazing history (semiarid/ subhumid x heavily grazed/lightly grazed), established them in pots in a common garden, and subjected the resulting plants to different combinations of drought and defoliation. Our results agreed with the convergence model. Aridity has selected T. crinita genotypes that respond better to drought and defoliation in terms of sexual reproduction and leaf growth, and that can evade grazing due to a lower shoot: root ratio and a higher resource allocation to reserves (starch) in stem bases. Similarly, grazing has selected genotypes that respond better to drought and defoliation in terms of sexual reproduction and that can evade grazing due to a lower digestibility of leaf blades. These results allow us to extend concepts of previous models in plant adaptation to herbivory to models on plant adaptation to drought. The only variable in which we obtained a result opposite to predictions was plant height, as plants from semiarid sites were taller (and with more erect tillers) than plants from subhumid sites; we hypothesize that this result might have been a consequence of the selection exerted by the high solar radiation and soil temperatures of semiarid sites. In addition, our work allows for the prediction of the effects of dry or wet growing seasons on the performance of T. crinita plants. Our results suggest that we can rely on dry environments for selecting grazing-resistant genotypes and on high grazing pressure history environments for selecting drought-resistant ones.

Corpus callosum abnormalities and the controversy about the candidate genes located in 1q44.

Submicroscopic deletions of 1q44-qter cause severe mental retardation, profound growth retardation, microcephaly and corpus callosum hypo/agenesis in most patients. At least 3 intervals in 1q44 have been described as critical regions containing genes leading to corpus callosum abnormalities. In this report we describe a patient with a de novo small interstitial 1q44 deletion of 1,152 kb detected with 44K oligonucleotide array-CGH (44K Agilent Technologies) and a mild phenotype lacking corpus callosum abnormalities. The first deleted oligonucleotide was located at 242.638 Mb (within the ADSS gene), and the last deleted oligonucleotide at 243.791 Mb (within the KIF26B gene). The clinical and molecular findings of the patient here reported remain consistent with a role for the AKT3 or ZNF238 genes in corpus callosum development.

Submicroscopic duplication of the Wolf-Hirschhorn critical region with a 4p terminal deletion.

Chromosomal rearrangements in the short arm of chromosome 4 can result in 2 different clinical entities: Wolf-Hirschhorn syndrome (WHS), characterized by severe growth delay, mental retardation, microcephaly, 'Greek helmet' facies, and closure defects, or partial 4p trisomy, associated with multiple congenital anomalies, mental retardation, and facial dysmorphisms. We present clinical and laboratory findings in a patient who showed a small duplication in 4p16.3 associated with a subtle terminal deletion in the same chromosomal region. GTG-banding analyses, multiplex ligation-dependent probe amplification analyses, and studies by array-based comparative genomic hybridization were performed. The results of the analyses revealed a de novo 1.3 Mb deletion of the terminal 4p and a 1.1 Mb duplication in our patient, encompassing the WHS critical region. Interestingly, this unusual duplication/deletion rearrangement results in an intermediate phenotype that shares characteristics of the WHS and the 4p trisomy syndrome. The use of novel technologies in the genetic diagnosis leads to the description of new clinical syndromes; there is a growing list of microduplication syndromes. Therefore, we propose that overexpression of candidate genes in WHS (WHSC1, WHSC2 and LETM1) due to a duplication causes a clinical entity different to both the WHS and 4p trisomy syndrome.

Sparse but not 'grandmother-cell' coding in the medial temporal lobe.

Although a large number of neuropsychological and imaging studies have demonstrated that the medial temporal lobe (MTL) plays an important role in human memory, there are few data regarding the activity of neurons involved in this process. The MTL receives massive inputs from visual cortical areas, and evidence over the last decade has consistently shown that MTL neurons respond selectively to complex visual stimuli. Here, we focus on how the activity patterns of these cells might reflect the transformation of visual percepts into long-term memories. Given the very sparse and abstract representation of visual information by these neurons, they could in principle be considered as 'grandmother cells'. However, we give several arguments that make such an extreme interpretation unlikely.

What is the real shape of extracellular spikes?

We show that the standard filters used for on-line spike detection in most hardware acquisition systems introduce distortions in the recorded spike shapes. This is because on-line spike detection is done after band pass filtering the data with causal filters. As illustrated with three clusters of spike shapes from a real single cell recording in a human subject, causal filtering can create a spurious negative rebound and a smooth looking appearance of the spikes. We also show that these filtering distortions can make artifacts look similar to real spikes.

Rare chromosomal complement of trisomy 21 in a boy conceived by IVF and cryopreservation.

This report describes a case of mosaic Down syndrome due to an unusual karyotype in a patient conceived by assisted reproductive techniques and cryopreservation. The chromosomal complement consists of two different cell lines, one predominantly trisomic with a derivative chromosome due to a Robertsonian translocation (21;21) and another carrying a ring chromosome 21. The present work analyses the different mechanisms that could have led to mosaicism.

Climatic niche shift in the amphitropical disjunct grass Trichloris crinita.

Plant species disjunctions have attracted the interest of ecologists for decades. We investigated Trichloris crinita, a native C4 perennial grass with disjunct distribution between subtropical regions of North and South America, testing the hypothesis that the species has a similar realized climatic niche in both subcontinents. The climatic niche of T. crinita in North and South America was characterized and compared using presence records and five uncorrelated bioclimatic variables selected according to their ecological importance for the species. We used reciprocal modeling to make geographic projections of the realized niche within each subcontinent. Niche overlap between T. crinita distributions in North and South America was intermediate for the individual climatic variables and the multivariate space. In all cases the test of equivalence between climates inhabited by T. crinita indicated that the realized niche of the species differ significantly between subcontinents. Also, the similarity test showed that in the majority of cases the realized niche in both subcontinents was significantly different than that expected by chance. T. crinita occupied a greater diversity of environments in South than in North America, while in the latter its distribution was displaced to drier and warmer environments. The modeled geographic distribution using the actual occurrences of the species in North America did not accurately predict the distribution in South America, and vice versa. Together, these results led us to reject the hypothesis of similar niche of T. crinita in both subcontinents. This information may be useful to manage restoration efforts by presenting the suitable areas and climates for the species, and suggesting that translocation of individuals between subcontinents could only be recommended with caution because introduced genotypes can be potentially maladaptive, and could colonize sites actually not occupied by the species within each subcontinent.

IL-2 effects on allogeneic and autologous transplant haemopoietic progenitors in long-term cultures.

IL-2 therapy may be useful in situations with a low tumour burden, such as after autologous transplantation. However, conflicting reports about the deleterious effects of this cytokine on haemopoiesis have precluded its widespread use. To study IL-2 effects on haemopoietic transplant progenitors we established long-term cultures (Dexter-type) with cells from allogeneic marrow and marrow/peripheral blood cell infusates of autologous transplants with different concentrations of IL-2 (0-1000 IU/ml). Percentage of CD56+ cells was also determined in cultures. IL-2 induced an inhibitory effect on stroma and an increase in the percentage of CD56+ cells compared with controls. No deleterious effect either in the production of BFU-E or CFU-GM weekly or over the whole period of culture was observed. Our results suggest that IL-2 is able to induce an increase in CD56+ cells early after transplantation without a deleterious effect on long-term haemopoiesis.

Bisensory stimulation increases gamma-responses over multiple cortical regions.

In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

Single-trial event-related potentials with wavelet denoising.

The application of a recently proposed denoising implementation for obtaining event-related potentials (ERPs) at the single-trial level is shown. We study its performance in simulated data as well as in visual and auditory ERPs. For the simulated data, the method gives a significantly better reconstruction of the single-trial event-related responses in comparison with the original data and also in comparison with a reconstruction based on conventional Wiener filtering. Moreover, with wavelet denoising we obtain a significantly better estimation of the amplitudes and latencies of the simulated ERPs. For the real data, the method clearly improves the visualization of both visual and auditory single-trial ERPs. This allows the calculation of better averages as well as the study of systematic or unsystematic variations between trials. Since the method is fast and parameter free, it could complement the conventional analysis of ERPs.

Functions and sources of event-related EEG alpha oscillations studied with the Wavelet Transform.

OBJECTIVES: By using the Wavelet Transform, a time frequency representation with nearly optimal resolution, we studied responses to stimulation in the 'alpha' range (10 Hz). METHODS: Visual evoked responses of 10 healthy subjects were studied with 3 different stimulus types (no-task VEP, non-target and target stimulus). RESULTS: Upon all the stimulus types, event-related responses in the 10 Hz ('alpha') range were distributed in the whole scalp, best defined in the occipital locations, the responses on the anterior electrodes being less pronounced and delayed. In some subjects, these event-related responses were prolonged upon target stimulation in posterior locations. CONCLUSIONS: These results point towards a distributed origin of event-related alpha oscillations with functional relation to sensory processing, and possibly to further processes.

Enhanced re-habituation of the orienting response of the human event-related potential.

Previous studies found the amplitude of the orienting response (OR) of the human event-related potential to decrease with repeated stimulus presentations. This decrease has been suggested to reflect short-term habituation and/or long-term habituation, both of which are learning processes. However, this earlier research failed to provide direct evidence supporting this claim. The present study attempted to show that the OR pattern shares one important feature of habituation: an enhanced response decrement across stimulus-presentation blocks (enhanced re-habituation). Participants received four blocks of 25 auditory stimulus presentations and showed an OR decrement both within (short-term habituation) and across (long-term habituation) blocks. Importantly, the OR decreased more rapidly during later than initial trial blocks, suggesting enhanced re-habituation. The latter result supports the notion that the amplitude decrement reflects an elementary learning process.