A novel approach for removing micro-stimulation artifacts and reconstruction of broad-band neuronal signals.

BACKGROUND: Electrical stimulation is a widely used method in the neurosciences with a variety of application fields. However, stimulation frequently induces large and long-lasting artifacts, which superimpose on the actual neuronal signal. Existing methods were developed for analyzing fast events such as spikes, but are not well suited for the restoration of LFP signals. NEW METHOD: We developed a method that extracts artifact components while also leaving the LFP components of the neuronal signal intact. We based it on an exponential fit of the average artifact shape, which is subsequently adapted to the individual artifacts amplitude and then subtracted. Importantly, we used for fitting of the individual artifact only a short initial time window, in which the artifact is dominating the superimposition with the neuronal signal. Using this short period ensures that LFP components are not part of the fit, which leaves them unaffected by the subsequent artifact removal. RESULTS: By using the method presented here, we could diminish the substantial distortions of neuronal signals caused by electrical stimulation to levels that were statistically indistinguishable from the original data. Furthermore, the effect of stimulation on the phases of γ- and ß- oscillations was reduced by 85 and 75 %, respectively. COMPARISON WITH EXISTING METHODS: This approach avoids signal loss as caused by methods cutting out artifacts and minimizes the distortion of the signal's temporal structure as compared to other approaches. CONCLUSION: The method presented here allows for a successful reconstruction of broad-band signals.

Optimizing the Yield of Multi-Unit Activity by Including the Entire Spiking Activity.

Neurophysiological data acquisition using multi-electrode arrays and/or (semi-) chronic recordings frequently has to deal with low signal-to-noise ratio (SNR) of neuronal responses and potential failure of detecting evoked responses within random background fluctuations. Conventional methods to extract action potentials (spikes) from background noise often apply thresholds to the recorded signal, usually allowing reliable detection of spikes when data exhibit a good SNR, but often failing when SNR is poor. We here investigate a threshold-independent, fast, and automated procedure for analysis of low SNR data, based on fullwave-rectification and low-pass filtering the signal as a measure of the entire spiking activity (ESA). We investigate the sensitivity and reliability of the ESA-signal for detecting evoked responses by applying an automated receptive field (RF) mapping procedure to semi-chronically recorded data from primary visual cortex (V1) of five macaque monkeys. For recording sites with low SNR, the usage of ESA improved the detection rate of RFs by a factor of 2.5 in comparison to MUA-based detection. For recording sites with medium and high SNR, ESA delivered 30% more RFs than MUA. This significantly higher yield of ESA-based RF-detection still hold true when using an iterative procedure for determining the optimal spike threshold for each MUA individually. Moreover, selectivity measures for ESA-based RFs were quite compatible with MUA-based RFs. Regarding RF size, ESA delivered larger RFs than thresholded MUA, but size difference was consistent over all SNR fractions. Regarding orientation selectivity, ESA delivered more sites with significant orientation-dependent responses but with somewhat lower orientation indexes than MUA. However, preferred orientations were similar for both signal types. The results suggest that ESA is a powerful signal for applications requiring automated, fast, and reliable response detection, as e.g., brain-computer interfaces and neuroprosthetics, due to its high sensitivity and its independence from user-dependent intervention. Because the full information of the spiking activity is preserved, ESA also constitutes a valuable alternative for offline analysis of data with limited SNR.

Attention Configures Synchronization Within Local Neuronal Networks for Processing of the Behaviorally Relevant Stimulus.

The need for fast and dynamic processing of relevant information imposes high demands onto the flexibility and efficiency of the nervous system. A good example for such flexibility is the attention-dependent selection of relevant sensory information. Studies investigating attentional modulations of neuronal responses to simultaneously arriving input showed that neurons respond, as if only the attended stimulus would be present within their receptive fields (RF). However, attention also improves neuronal representation and behavioral performance, when only one stimulus is present. Thus, attention serves for selecting relevant input and changes the neuronal processing of signals representing selected stimuli, ultimately leading to a more efficient behavioral performance. Here, we tested the hypothesis that attention configures the strength of functional coupling between a local neuronal network's neurons specifically for effective processing of signals representing attended stimuli. This coupling is measured as the strength of γ-synchronization between these neurons. The hypothesis predicts that the pattern of synchronization in local networks should depend on which stimulus is attended. Furthermore, we expect this pattern to be similar for the attended stimulus presented alone or together with irrelevant stimuli in the RF. To test these predictions, we recorded spiking-activity and local field potentials (LFP) with closely spaced electrodes in area V4 of monkeys performing a demanding attention task. Our results show that the γ-band phase coherence (γ-PhC) between spiking-activity and the LFP, as well as the spiking-activity of two groups of neurons, strongly depended on which of the two stimuli in the RF was attended. The γ-PhC was almost identical for the attended stimulus presented either alone or together with a distractor. The functional relevance of dynamic γ-band synchronization is further supported by the observation of strongly degraded γ-PhC before behavioral errors, while firing rates were barely affected. These qualitatively different results point toward a failure of attention-dependent top-down mechanisms to correctly synchronize the local neuronal network in V4, even though this network receives the correctly selected input. These findings support the idea of a flexible, demand-dependent dynamic configuration of local neuronal networks, for performing different functions, even on the same sensory input.

Biochemical characterization of trans-sialidase TS1 variants from Trypanosoma congolense.

BACKGROUND: Animal African trypanosomiasis, sleeping sickness in humans and Nagana in cattle, is a resurgent disease in Africa caused by Trypanosoma parasites. Trans-sialidases expressed by trypanosomes play an important role in the infection cycle of insects and mammals. Whereas trans-sialidases of other trypanosomes like the American T. cruzi are well investigated, relatively little research has been done on these enzymes of T. congolense. RESULTS: Based on a partial sequence and an open reading frame in the WTSI database, DNA sequences encoding for eleven T. congolense trans-sialidase 1 variants with 96.3% overall amino acid identity were amplified. Trans-sialidase 1 variants were expressed as recombinant proteins, isolated and assayed for trans-sialylation activity. The purified proteins produced α2,3-sialyllactose from lactose by desialylating fetuin, clearly demonstrating their trans-sialidase activity. Using an HPLC-based assay, substrate specificities and kinetic parameters of two variants were characterized in detail indicating differences in substrate specificities for lactose, fetuin and synthetic substrates. Both enzymes were able to sialylate asialofetuin to an extent, which was sufficient to reconstitute binding sites for Siglec-4. A mass spectrometric analysis of the sialylation pattern of glycopeptides from fetuin revealed clear but generally similar changes in the sialylation pattern of the N-glycans on fetuin catalyzed by the trans-sialidases investigated. CONCLUSIONS: The identification and characterization of a trans-sialidase gene family of the African parasite T. congolense has opened new perspectives for investigating the biological role of these enzymes in Nagana and sleeping sickness. Based on this study it will be interesting to address the expression pattern of these genes and their activities in the different stages of the parasite in its infection cycle. Furthermore, these trans-sialidases have the biotechnological potential to be used for enzymatic modification of sialylated glycoconjugates.