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Eitan, R.

Publications and source records attributed to Eitan, R..

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Human Subthalamic Nucleus Selectively Decreases its Response to the Go-Signal in a Motor Inhibition Context

To better understand the mechanism of movement facilitation and inhibition in the subthalamic nucleus (STN), we recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (n=43 patients, 173 sites) performed increasingly complex oddball paradigms: auditory ( None-Go, n=7, 28), simple movement ( All-Go, n=7, 26) and movement inhibition ( Go-NoGo, n=29, 119) tasks. To enable physiological sampling of the different subthalamic nucleus domains in both hemispheres, each patient performed one of the oddball paradigms several times.\n\nThe human STN responded mainly to movement-involving tasks: movement execution at the motor STN and movement planning at the limbic-associative STN. In the limbic-associative STN, responses to the inhibitory cue (deviant tone) in the movement inhibition task were not significantly different from the simple movement task. However, responses to the go cue (frequent tone) were significantly reduced. The reduction was mainly in the negative component of the evoked response amplitude. Successful movement inhibition was correlated with higher baseline activity before the inhibitory cue.\n\nWe suggest that the STN adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the associative-limbic domains in movement planning and in global movement regulation.

neuroscience

Reconstructing cancer karyotypes from short read data: the half full and half empty glass

BackgroundDuring cancer progression genomes undergo point mutations as well as larger segmental changes. The latter include, among others, segmental deletions duplications, translocations and inversions. The result is a highly complex, patient-specific cancer karyotype. Using high-throughput technologies of deep sequencing and microarrays it is possible to interrogate a cancer genome and produce chromosomal copy number profiles and a list of breakpoints (\"jumps\") relative to the normal genome. This information is very detailed but local, and does not give the overall picture of the cancer genome. One of the basic challenges in cancer genome research is to use such information to infer the cancer karyotype.\n\nWe present here an algorithmic approach, based on graph theory and integer linear programming, that receives segmental copy number and breakpoint data as input and produces a cancer karyotype that is most concordant with them. We used simulations to evaluate the utility of our approach, and applied it to real data.\n\nResultsBy using a simulation model, we were able to estimate the correctness and robustness of the algorithm in a spectrum of scenarios. Under our base scenario, designed according to observations in real data, the algorithm correctly inferred 69% of the karyotypes. However, when using less stringent correctness metrics that account for incomplete and noisy data, 87% of the reconstructed karyotypes were correct. Furthermore, in scenarios where the data were very clean and complete, accuracy rose to 90%-100%. Some examples of analysis of real data, and the karyotypes reconstructed by our algorithm, are also presented.\n\nConclusionWhile reconstruction of complete, perfect karyotype based on short read data is very hard, a large portion of the reconstruction will still be correct and can provide useful information.

bioinformatics