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Stereoelectroencephalography (SEEG) in children with intractable epilepsy presents particular challenges. Their thin and partially ossified cranium, specifically in the temporal area, is prone to fracture while attaching stereotactic systems to the head or stabilizing the head in robot’s field of action. Postponing SEEG in this special population of patients can have serious consequences, reducing their chances of becoming seizure-free and impacting their social and cognitive development. This study demonstrates the safety and accuracy offered by a frameless personalized 3D printed stereotactic implantation system for SEEG investigations in children under 4 years of age. SEEG was carried out in a 3-year-old patient with drug-resistant focal epilepsy, based on a right temporal-perisylvian epileptogenic zone hypothesis. Fifteen intracerebral electrodes were placed using a StarFix patient-customized stereotactic fixture. The median lateral entry point localization error of the electrodes was 0.90 mm, median lateral target point localization error was 1.86 mm, median target depth error was 0.83 mm, and median target point localization error was 1.96 mm. There were no perioperative complications. SEEG data led to a tailored right temporal-insular-opercular resection, with resulting seizure freedom (Engel IA). In conclusion, patient-customized stereotactic fixtures are a safe and accurate option for SEEG exploration in young children.

OBJECTIVE: Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization.METHODS: We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM - N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach.RESULTS: Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep.CONCLUSIONS: Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity.SIGNIFICANCE: We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.

Background Stereoelectroencephalograpy (SEEG) is a diagnostic method involving 3-dimensional exploration of brain structures using depth electrodes for locating epileptogenic foci in patients with drug-resistant epilepsy. A variety of frame-based, frameless, and robotic stereotactic systems have been designed for the accurate placement of depth electrodes. Objectives Using the FHC microTargeting platform as a model, we introduce a fully customized design that has all the constructive elements positioned by a computer algorithm, according to the planned trajectories, anchoring points, and anatomic constraints. All the constructive elements form a single-body fixture, which allows for the efficient implantation of multiple depth electrodes following trajectories having a wide range of orientations. We aim at evaluating the safety and accuracy of this stereotactic system in a clinical setting. Methods A total of 173 depth electrodes were implanted in 21 patients with drug-resistant epilepsy. Matlab and DEETO software packages were used to postoperatively evaluate the targeting accuracy. Automatic detection of electrode locations eliminated any subjectivity in calculating the targeting errors. Results As a result of using custom geometry of the stereotactic platform, the new design is optimized for each patient and streamlines the surgical procedures. The most important results characterizing the platform's accuracy are the values of 1.22 mm for the median lateral target point localization error and 1.17 mm for the median lateral entry point localization error. Conclusions The patient-customized platforms are comparable in terms of safety, accuracy, and simplicity of use to the existing robotic devices for implantation of depth electrodes in patients undergoing SEEG investigations.

BACKGROUND Chronic migraine (CM) is a highly debilitating disease, and many patients remain refractory to medicinal therapy. Given the convergent nature of neuronal networks in the ventral posteromedial nucleus (VPM) and the evidence of sensitization of pain circuitry in this disease, we hypothesize CM rats will have increased VPM neuronal firing, which can be attenuated using occipital nerve stimulation (ONS). OBJECTIVE To determine whether VPM firing frequency differs between CM and sham rats, and whether ONS significantly alters firing rates during the application of mechanical stimuli. METHODS Fourteen male Sprague-Dawley rats were infused with inflammatory media once daily through an epidural cannula for 2 wk to induce a CM state. Sham animals (n = 6) underwent cannula surgery but received no inflammatory media. ONS electrodes were implanted bilaterally and single-unit recordings were performed in the VPM of anesthetized rats during mechanical stimulation of the face and forepaw in the presence and absence of ONS. RESULTS CM rats had significantly higher neuronal firing rates (P < .001) and bursting activity (P < .01) in response to mechanical stimuli when compared to shams. ONS significantly reduced neuronal firing in the VPM of CM rats during the application of 0.8 g (P = .04), 4.0 g (P = .04), and 15.0 g (P = .02) Von Frey filaments. ONS reduced bursting activity in CM rats during the 4.0 and 15 g filaments (P < .05). No significant changes in bursting activity or firing frequency were noted in sham animals during ONS. CONCLUSION We demonstrate that neuronal spike frequencies and bursting activity in the VPM are increased in an animal model of CM compared to shams. Our results suggest that the mechanism of ONS may involve attenuation of neurons in the VPM of CM rats during the application of mechanical stimuli.

High-frequency oscillations >80 Hz (HFOs) have unique features distinguishing them from spikes and artifactual components that can be well-evidenced in the time-frequency representations. We introduce an unsupervised HFO detector that uses computer-vision algorithms to detect HFO landmarks on two-dimensional (2D) time-frequency maps. To validate the detector, we introduce an analytical model of the HFO based on a sinewave having a Gaussian envelope, for which analytical equations in time-frequency space can be derived, allowing us to establish a direct correspondence between common HFO detection criteria in the time domain with the ones in the frequency domain, used by the computer-vision detection algorithm. The detector identifies potential HFO events on the time-frequency representation, which are classified as true HFOs if criteria regarding the HFO's frequency, amplitude, and duration are met. The detector is validated on simulated HFOs according to the analytical model, in the presence of noise, with different signal-to-noise ratios (SNRs) ranging from −9 to 0 dB. The detector's sensitivity was 0.64 at an SNR of −9 dB, 0.98 at −6 dB, and >0.99 at −3 dB and 0 dB, while its positive prediction value was >0.95, regardless of the SNR. Using the same simulation dataset, our detector is benchmarked against four previously published HFO detectors. The F-measure, a combined metric that takes into account both sensitivity and positive prediction value, was used to compare detection algorithms. Our detector surpassed the other detectors at −6, −3, and 0 dB and had the second best F-score at −9 dB SNR after the MNI detector (0.77 vs. 0.83). The ability to detect HFOs in clinical recordings has been tested on a set of 36 intracranial electroencephalogram (EEG) channels in six patients, with 89% of the detections being validated by two independent reviewers. The results demonstrate that the unsupervised detection of HFOs based on their 2D features in time-frequency maps is feasible and has a performance comparable or better than the most used HFO detectors.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug‐resistant epilepsy, explored by stereo‐electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high‐frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h (2) coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi‐body. High‐frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.

Background Initial subthalamic nucleus (STN) localization is based on MRI and an anatomical atlas and then refined intraoperatively using electrophysiological mapping with microelectrode recordings (IOA – intraoperative multi-unit activity) during deep brain stimulation (DBS) in Parkinson's disease (PD). IOA is time consuming and subjective. The purpose of this study was to assess the value of high frequency multi-unit background activity (MUA, frequency > 500 Hz), and local field potentials (LFP, frequency 5–500 Hz) in detection of the STN borders. Methods This was a retrospective, single center study. 18 leads in ten PD patients that underwent STN DBS surgery were evaluated. IOA, MUA and LFP have been compared in detection of the STN. IOA using single train spikes analysis have been used as a gold standard. Results Both LFP in beta range (20–35 Hz) and MUA increased as the microelectrode entered the STN and their increase correlated with dorsal/ventral STN borders. The differences (mean ± sd) were: between IOA and MUA of the dorsal/ventral border 0.20 ± 0.76/0.28 ± 0.30 mm; between IOA and LFP of the dorsal/ventral border 0.08 ± 0.94/0.05 ± 0.53 mm. Using Bland–Altman statistics, only 2 / 36 (5.6%) differences between IOA and MUA and also 2 / 36 differences between IOA and LFP (one for the dorsal border and one for the ventral border) were out of ± 1.96 SD line of measurement differences. Correlation between dorsal border/ventral border positions obtained by IOA and MUA was 0.86, p Conclusions Both MUA and LFP are characteristically elevated in the STN compared to neighboring structures. They may provide fast, real-time, objective and reliable markers of STN borders.

Objectives Intracranial direct electrical stimulation (iDES) uses different parameters for mapping the epileptogenic and functional areas in patients with drug-resistant epilepsy. We aim at finding the common factor driving the electrographic responses to various iDES protocols reported in the literature. Methods We recorded early responses to single-pulse iDES in 11 subjects undergoing stereoelectroencephalographic presurgical evaluation. We systematically explored the role of several pulse parameters in evoking responses: monophasic versus biphasic pulses, current intensity, and pulse duration. We performed a correlation and regression analysis between responses to different protocols by amplitude, duration, and charge per phase. Results Regression analysis revealed that the responses were similar for the same charge per phase, regardless of their pulse duration and amplitude. Over eighty percent (82.8%) of the responses to variable pulse duration biphasic stimulation and between 58.6% and 81.9% of the responses to monophasic stimulation, depending on pulse polarity, were correlated to the responses evoked by the variable amplitude biphasic protocol, when expressing stimulus strength in terms of charge per phase. Conclusions Regardless of the combination of different stimulation currents, it is the underlying charge per phase parameter that determines the magnitude of the responses to single-pulse electrical stimulation. Significance Our results provide a unifying method for comparing iDES protocols.

Background Temporal lobe epilepsy is frequently improved after selective resection. However, a small number of these patients have temporal-plus epilepsy and continue seizing. We aim to study the connectivity of the temporal lobe during wakefulness and sleep. Material and methods We included 25 patients with drug-resistant focal epilepsy who had depth electrodes exploration in 2016–2018. We implanted 9–18 electrodes per patient over a large network. We performed single pulse electrical stimulation protocol, as previously described, during wakefulness and sleep. We selected 40,678 statistically significant responses (rho > 0.4, p Results The difference between the mean responses in all temporal structures between sleep and wakefulness is 10.41 μV (p Conclusions Temporal lobe connectivity is modulated by sleep, EZ location, and pertainence of certain structures to the EZ, with statistically significant differences between left and right temporal structures.

International audience; Objective: Technology for localizing epileptogenic brain regions plays a central role in surgical planning. Recent improvements in acquisition and electrode technology have revealed that high-frequency oscillations (HFOs) within the 80-500 Hz frequency range provide the neurophysiologist with new information about the extent of the epileptogenic tissue in addition to ictal and interictal lower frequency events. Nevertheless, two decades after their discovery there remain questions about HFOs as biomarkers of epileptogenic brain and there use in clinical practice.Methods: In this review, we provide practical, technical guidance for epileptologists and clinical researchers on recording, evaluation, and interpretation of ripples, fast ripples, and very high-frequency oscillations.Results: We emphasize the importance of low noise recording to minimize artifacts. HFO analysis, either visual or with automatic detection methods, of high fidelity recordings can still be challenging because of various artifacts including muscle, movement, and filtering. Magnetoencephalography and intracranial electroencephalography (iEEG) recordings are subject to the same artifacts.Significance: High-frequency oscillations are promising new biomarkers in epilepsy. This review provides interested researchers and clinicians with a review of current state of the art of recording and identification and potential challenges to clinical translation.

Pre surgical evaluation in drug resistant epilepsy is based also on invasive EEG recordings in order to accurately establish the epileptogenic zone for surgical resection as well as the eloquent cortex that should be spared. During intracranial session we record ictal events and we apply different stimulation protocols to study functional cortex. In our centre we use the stereo-EEG method to identify the epileptogenic networks and mainly high frequency (50 Hz) stimulation for cortical mapping. By modulating the properties of the stimulation waveforms, in conjunction with the nonlinear response of the tissue to electrical stimulation, we were able to recover the physiological responses during the course of the stimulation train. The activation of the networks at stimulation levels evoking a clinical symptom was compared with the below-threshold stimulation, that did not elicit any clinical effects, allowing to evidence a selective recruitment of pathways associated with a particular symptom. The method is used for identification of physiologic networks associated with various somatosensory, motor or language-related symptoms, to investigate the impact of epileptogenic zone to functional cortex as well as to predict a possible post surgical deficit.

Object Insight may be gained into the physiological mechanisms of deep brain stimulation (DBS) by analyzing local and contralateral subthalamic nucleus (STN) single-unit activity during activation of previously placed DBS electrodes. Special techniques are required to perform such analysis due to the presence of a large stimulus artifact. The purpose of this study was to determine the effects of DBS stimulation on single unit activity acquired from patients undergoing new or revised DBS placements. Methods Subthalamic nucleus single unit activity was acquired from awake patients during activation of a previously implanted STN DBS electrode. Stimulation was contralateral to the recording site in 4 cases and ipsilateral in 3. Data were acquired at stimulation frequencies of 30, 60, and 130 Hz and with other stimulation parameters at clinically effective settings. Cells were included if they showed kinesthetic activity before and after the stimulation paradigm and if their action potential morphology was maintained throughout the experiment. Analysis of single-unit activity acquired before, during, and after stimulation was performed employing a time-domain algorithm to overcome the stimulus artifact. Results Both ipsilateral and contralateral acute stimulation resulted in reversible STN firing rate suppression. The degree of suppression became greater as stimulus frequency increased and was significant at 60 Hz (t-test, p < 0.05) and 130 Hz (p < 0.01). Suppression with ipsilateral 130-Hz stimulation ranged between 52.8% and 99.8%, whereas with similar contralateral STN stimulation, the range was lower (1.9%–50.3%). Return to baseline activity levels typically occurred within seconds after stimulation ended. Conclusions Stimulation of the STN at clinically effective frequencies has an acute suppressive rather than an excitatory effect on STN single-unit activity. The effect is bilateral, even though the degree of suppression is greater on the ipsilateral than the contralateral STN. The authors' algorithm helps reveal this effect in human patients.

Objective We aim to study the connections of the posterior insula (pI) and anterior insula (aI) through cortico-cortical evoked potentials (CCEP) by single pulse electrical stimulation (SPES). Method We performed SPES stimulation protocol in a group of 8 refractory epilepsy patients presurgically explored with intracerebral depth electrodes, out of which 6 were operated on and are currently seizure-free. We selected the early responses (ER) obtained from contacts of 24 electrodes that were included in the anterior and posterior insula, when this structure was outside the seizure onset zone (SOZ). Responses were analyzed in terms of amplitude variations during wakefulness and sleep. Effective connectivity betweeen cortical was calculated based on the measured CCEPs. Results The ER amplitudes by SPES stimulation in the insula during wakefulness compared to sleep showed statistically significant ( p 0.05 ) differences in 6 patients. There are constant connections between aI and pI. We identified connectivity of the pI with language-related brain stuctures during wakefulness, and with the temporal mesial structures during sleep, possibly influenced by the SOZ. Right pI stimulation seems to elicit ampler reponses in the rolandic operculum and parietal structures during wakefulness, and in the primary motor and premotor cortex during sleep. Anterior insula has preferential connectivity with anterior cingulate gyrus during wakefulness and with the fusiform gyrus during sleep. Discussions Connectivity of the aI versus pI, as well as right versus left insula during wakefulness and sleep is different, partially supporting previous observations. Conclusion Sleep has been shown to alter the physiological connectivity of the insula. Further investigations are in progress to confirm these results. Significance These findings describe insular connectivity and variability during sleep, with possible implications in epilepsy surgery, sleep disorders understanding and language studies.

Magnetic resonance imaging (MRI)-negative epilepsy may be successfully solved with a multidisciplinary approach using invasive recordings, image and signal analysis. The whole methodology used by the epilepsy surgery team is systematically described based on an resistant epilepsy case with all steps and rationale of choosing different investigation methods from surface electroencephalography (EEG) to invasive recordings. Due to negative MRI and non-concordant ictal surface EEG with clinical semiology, the patient was investigated with stereo- EEG (SEEG), aiming to delimitate epileptogenic and eloquent cerebral areas. Implantation strategy, seizures recordings, stimulation, resection planning using quantitative EEG analysis, and the surgery plan are presented. The patient has been seizure-free for 14 months so far, with improved behavior and daily life quality. Post-operative examination revealed focal cortical dysplasia type II B.

Epileptic seizures are characterized by a rich dynamic spectrum consisting of excessive, abnormal and synchronized firing of neuron ensembles. Such abnormal firing has been quantitatively characterized via power laws in neural avalanches. The term “neural avalanche” has been used to illustrate the excessively amplified neural firing patterns that lead to epileptic seizures. The pattern of amplified firing in neural avalanches betrays a modular signature in the spread of activation across cortical minicolumns. According to this modular approach of epilepsy, the excessive amplification of neural firing in a cortical minicolumn results from a defect within the “inhibitory curtain” surrounding the pyramidal cells. The functional basis of this approach provides insights into potential clinical interventions.

A new laser method is proposed for the deposition of high purity, hard fcc TiN layers of unlimited thickness. The film thickness can be very finely controlled mainly through the intermediary of the number of applied laser pulses as the deposition rate is of only 0.02–0.05 nm/pulse. The ablation is promoted from a Ti target by high intensity multipulse excimer laser irradiation in a low pressure N2 ambient gas while the forming compound is collected on a Si single‐crystalline wafer. The best results have been obtained for an ambient pressure of p=10–30 mTorr and a distance between the target and support of d=10 mm. It is shown that the formation of a liquid phase within the irradiated zone, maintained even after the end of a laser pulse, is the most important requisite for TiN formation. TiN is then ablated as a stoichio‐ metric phase.

Objectives To assess the role of signal analysis methods for accurate delineation of the epileptogenic zone during surgery for drug resistant epilepsy. Methods We used surface video EEG as well as invasive studies by means of the stereo-EEG method to identify the epileptogenic networks. Signal analysis tools have been applied systematically during pre surgical evaluation to study ictal as well as interictal activity and responses to different stimulation protocols. Connectivity charts were computed based on analysis of cortico-cortical evoked potentials on single pulse electrical stimulation (SPES). The results were interpreted according with an individual patient hypothesis and integrated with clinical and anatomic data. Results We explored 63 patients at the University Hospital of Bucharest in the National Program for Epilepsy Surgery between 2012 and 2016 of which 57 received either open surgeries or undergone a procedure of radio frequency thermocoagulation (RFTC) applied on intracranial electrodes. In the group of patients ( n = 34) with more than 2 years follow up after surgery, 25 (74%) are seizure free. Signal post processing analysis was critical for surgical planning in 12 cases (48%). Discussion Systematic use of signal analysis approach improved the definition of surgical resection limits, made the recording sessions shorter without sacrificing information, and allowed a better definition of targets for RFTC protocols during SEEG recordings. Conclusion Signal analysis tools added complementary information where the traditional visual analysis was not helpful for surgical planning. Significance Post processing methods of the EEG signal integrated with the anatomo-clinical hypothesis offer unbiased valuable data to improve surgical outcome.

Objectives In deep comatose states, the EEG appears discontinuous, consisting of bursts of activity on a flat electrical background referred to as the burst-suppression (BS) pattern. We aimed to develop a quantitative EEG measure that can be applied to both BS and continuous EEG coma. Methods We recoded EEG changes in response to intermittent photic or electrical nerve stimulation epochs lasting 1 min. The multi-channel EEG was reduced to a binary signal of alternating stimulus processing and default classes. A default class ratio could then be defined for continuous EEG by analogy with the suppression ratio of BS. A global EEG reactivity index was derived to measure the relative reduction in default class ratio during (effects) and immediately following stimulation (after-effects). Results We found that in patients with BS coma, the EEG reactivity index correlated with clinical coma evaluation and prognostication scales. The same reactivity index measured during BS induced by general anesthesia, was found to reflect the degree of brain injury in experimental rodent models. Ongoing studies indicate that the EEG reactivity index also correlates with the clinical severity of coma with continuous EEG. Discussion Our data suggest that during BS, the bursts reflect stimulus-evoked activity whereas the suppression reflects the missing default activity. Conclusions We propose a novel EEG reactivity index that can be measured in BS and continuous EEG coma alike. Significance Our EEG reactivity index could provide a continuous measure for monitoring recovery from coma and the post-comatose disorders of consciousness. This work was supported by grants of the Romanian National Authority for Scientific Research, CNCS – UEFISCDI, project number PN-II-ID-PCE-2011-3-0847, PN-II-PT-PCCA-2011-3.2-1290 and PN-III-P2-2.1-PTE-2016-0114 to MM.

Background: The stereoelectroencephalographic (SEEG) implantation procedures still represent a challenge due to the intrinsic complexity of the method and the number of depth electrodes required. Objectives: We aim at designing and evaluating the accuracy of a custom stereotactic fixture based on the StarFix™ technology (FHC Inc., Bowdoin, ME) that significantly simplifies and optimizes the implantation of depth electrodes used in presurgical evaluation of patients with drug-resistant epilepsy. Methods: Fiducial markers that also serve as anchors for the fixture are implanted into the patient's skull prior to surgery. A 3D fixture model is designed within the surgical planning software, with the planned trajectories incorporated in its design, aligned with the patient's anatomy. The stereotactic fixture is built using 3D laser sintering technology based on the computer-generated model. Bilateral rectangular grids of guide holes orthogonal to the midsagittal plane and centered on the midcommissural point are incorporated in the fixture design, allowing a wide selection of orthogonal trajectories. Up to two additional grids can be accommodated for targeting structures where oblique trajectories are required. The frame has no adjustable parts, this feature reducing the risk of inaccurate coordinate settings while simultaneously reducing procedure time significantly. Results: We have used the fixture for the implantation of depth electrodes for presurgical evaluation of 4 patients with drug-resistant focal epilepsy, with nearly 2-fold reduction in the duration of the implantation procedure. We have obtained a high accuracy with a submillimetric mean positioning error of 0.68 mm for the anchor bolts placed at the trajectory entry point and 1.64 mm at target. Conclusions: The custom stereotactic fixture design greatly simplifies the planning procedure and significantly reduces the time in the operating room, while maintaining a high accuracy.

A numerical analysis is performed of the laser heating of metallic thin films deposited on electron microscope copper grids. A quasiuniform heating is predicted for the central zones within grid meshes, followed by a cooling with significantly different rates, depending on the analyzed point location relative to the grid mesh edge. This behavior is found to be in good agreement with the experimental evidence of the laser treated zones, as provided by electron microscopy investigation followed by a Fourier analysis of the recorded images.

It is assumed that the acoustic waves induced by the high-intensity laser irradiation of various substrates can intervene in the formation of surface structures within and outside the laser irradiation spot. An experiment was designed and performed which appropriately allows for checking up this hypothesis and a correlation is evidenced between the geometrical characteristics of the forming surface structure and the parameters, first of all frequency, of surface acoustic waves.

a Stereoelectroencephalographic 3-D mapping of epileptogenicity using responses to single-pulse electrical stimulation Cristian Donos1 , Ioana Mindruta4,5, Jean Ciurea3, Alin Rasina3, Mihai Dragos Malaia5 ,Andrei Barborica1,2 1 Physics Department, University of Bucharest, Bucharest, Romania, 2 FHC Inc, Bowdoin ME, USA, 3 Neurosurgery Department, Bagdasar-Arseni Hospital, Bucharest, Romania, 4 Neurology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, 5 Neurology Department, University Emergency Hospital, Bucharest, Romania

An internal model for predictive saccades in frontal cortex was investigated by recording neurons in monkey frontal eye field (FEF) during an inferred motion task. Monkeys were trained to make saccades to the extrapolated position of a small moving target that was rendered temporarily invisible and whose trajectory was altered. On approximately two-thirds of the trials, monkeys made multiple saccades while the target was invisible. Primary saccades were correlated with extrapolated target position. Secondary saccades significantly reduced residual errors resulting from imperfect accuracy of the first saccade. These observations suggest that the second saccade was corrective. Because there was no visual feedback, corrective saccades could only be driven by an internally generated error signal. Neuronal activity in the frontal eye field was directionally tuned before both primary and secondary saccades. Separate subpopulations of cells encoded either saccade direction or direction error before the second saccade. These results suggest that FEF neurons encode the error after the first saccade, as well as the direction of the second saccade. Hence, FEF appears to contribute to detecting and correcting movement errors based on internally generated signals.

The purpose of this study was to investigate the interaction between internal representations of invisible moving targets and visual responses of neurons in frontal eye fields (FEFs). Monkeys were trained to make saccades to the extrapolated position of a target that was temporarily rendered invisible for variable durations as if it had passed behind an occluder. Flashed, task-irrelevant visual probe stimuli were used to study the visual responsiveness of FEF neurons during this task. Probes were flashed at various times and locations during the occlusion interval. Net changes in neuronal activity were obtained by comparing the activity on trials with probes with randomly interleaved trials without any probe. Most neurons showed an increase in firing rate in response to the probe, but some showed a decrease. Both types of responses were enhanced when the invisible target moved toward the receptive field (RF) as compared with trials on which the target moved away from the RF. Some neurons showed a spatial shift in the visual response during the occlusion interval. For cells that were excited by the probe, the shift tended to be correlated with the direction of motion of the target, whereas for cells that were inhibited the shift tended to be in the opposite direction. These results suggest that the role of FEF in predicting invisible target motion includes a sensory/perceptual component.

Working memory involves transient storage of information and the ability to manipulate that information for short-range planning and prediction. The computational aspect of working memory can be probed using dynamic sensorimotor behavior requiring complex stimulus-response mappings. Such a transformation occurs when extrapolating the future location of a moving target that is rendered temporarily invisible. Estimating the trajectory of an invisible moving target requires encoding and storing several target features, including the direction and speed of motion. We trained monkeys to make saccades to the estimated position of invisible targets moving at various speeds. The activity of neurons in the frontal eye field (FEF) was consistently modulated according to the speed of target motion. A reconstruction algorithm showed that estimates of target speed based on FEF activity were similar to behavioral speed estimates. FEF may therefore be involved in updating an internal representation of target trajectory for predictive saccades.

We introduce a new theoretical analysis of the temporal and spatial evolution of surface topography of solids following interference between incident and scattered pulsed laser beams. The essential role played by the nonlinear delayed feedback in the laser radiation-surface system is considered. We show that it finally determines the surface topography evolution from pulse to pulse. In order to complete the analysis, numerical calculations have been conducted under the hypothesis of strong attenuation of laser radiation into the sample and of a limited heat diffusion during the action of a laser pulse. We predict an evolution from very simple to complex (chaotic) structures under multipulse laser irradiation of solid surfaces. This evolution is determined by some key irradiation parameters--initial surface microrelief, incident laser intensity and the number of applied laser pulses. Experiments were performed in order to check-up the main predictions of the theoretical analysis. The system TEA-CO 2 laser radiation ((lambda) equals 10.6 micrometers )--fused silica was chosen as appropriate for performing test experiments. Optical microscopy studies of laser treated zones evidenced special modifications of the surface topography in good accordance with the conclusions following from the theoretical analysis. The theoretical analysis is also in good agreement with some available data from literature, at the same time providing a coherent interpretation of previously unexplained behaviors.

High power laser pulse irradiation of material surfaces produces a wide spectrum of phenomena, all connected with emerging new technologies. Topics like: ablation, thin films deposition, laser induced chemical reaction are frequently studied. Few studies have been reported in the domain of laser induced solid state phase transitions at -a relative low laser fluence. In this regime the laser pulse acting like a high power heat pulse, the evolution of the system is far from equilibrium and new structures or new mechanism of transformation is expected.

Spatially selective delay activity in the frontal eye field (FEF) is hypothesized to be part of a mechanism for the transformation of visual signals into instructions for voluntary movements. To understand the linkage between FEF activity and eye movement planning, we recorded neuronal responses of FEF neurons while monkeys performed a memory-saccade task. We then electrically stimulated the same sites during the memory-delay epoch of the task. The stimulation currents used were subthreshold for evoking saccades during a gap-fixation task. Microstimulation resulted in changes in the spatial and temporal components of saccade parameters: an increase in latency, and a shift in amplitude and direction. We performed a vector analysis to determine the relative influence of the visual cue and electrical stimulus on the memory-saccade. In general, the memory-saccade was strongly weighted toward the visual cue direction, yet the electrical stimulus introduced a consistent bias away from the receptive/movement field of the stimulation site. The effects of sub-threshold stimulation were consistent with a combination of vector subtraction and averaging, but not with vector summation. Vector subtraction may play a role in spatial updating of movement plans for memory-guided saccades when eye position changes during the memory period.

Keeping pace with a constantly changing world requires the ability to make predictions about the future on a variety of timescales. A very basic example of this is the ability to predict the future location of a moving object in the brief time that it takes to perceive and respond to that object. In this issue of Neuron, experiments by Sundberg, Fallah, and Reynolds reveal a potential neural substrate for making short-range predictions about motion in visual area V4.