Parallelized Acquisition of Orbitrap and Astral Analyzers Enables High-Throughput Quantitative Analysis.

The growing trend toward high-throughput proteomics demands rapid liquid chromatography-mass spectrometry (LC-MS) cycles that limit the available time to gather the large numbers of MS/MS fragmentation spectra required for identification. Orbitrap analyzers scale performance with acquisition time and necessarily sacrifice sensitivity and resolving power to deliver higher acquisition rates. We developed a new mass spectrometer that combines a mass-resolving quadrupole, the Orbitrap, and the novel Asymmetric Track Lossless (Astral) analyzer. The new hybrid instrument enables faster acquisition of high-resolution accurate mass (HRAM) MS/MS spectra compared with state-of-the-art mass spectrometers. Accordingly, new proteomics methods were developed that leverage the strengths of each HRAM analyzer, whereby the Orbitrap analyzer performs full scans with a high dynamic range and resolution, synchronized with the Astral analyzer's acquisition of fast and sensitive HRAM MS/MS scans. Substantial improvements are demonstrated over previous methods using current state-of-the-art mass spectrometers.

Inter-trial phase coherence of visually evoked postural responses in virtual reality.

Vision plays a central role in maintaining balance. When humans perceive their body as moving, they trigger counter movements. This results in body sway, which has typically been investigated by measuring the body's center of pressure (COP). Here, we aimed to induce visually evoked postural responses (VEPR) by simulating self-motion in virtual reality (VR) using a sinusoidally oscillating "moving room" paradigm. Ten healthy subjects participated in the experiment. Stimulation consisted of a 3D-cloud of random dots, presented through a VR headset, which oscillated sinusoidally in the anterior-posterior direction at different frequencies. We used a force platform to measure subjects' COP over time and quantified the resulting trajectory by wavelet analyses including inter-trial phase coherence (ITPC). Subjects exhibited significant coupling of their COP to the respective stimulus. Even when spectral analysis of postural sway showed only small responses in the expected frequency bands (power), ITPC revealed an almost constant strength of coupling to the stimulus within but also across subjects and presented frequencies. Remarkably, ITPC even revealed a strong phase coupling to stimulation at 1.5 Hz, which exceeds the frequency range that has generally been attributed to the coupling of human postural sway to an oscillatory visual scenery. These findings suggest phase-locking to be an essential feature of visuomotor control.

Multiunit Frontal Eye Field Activity Codes the Visuomotor Transformation, But Not Gaze Prediction or Retrospective Target Memory, in a Delayed Saccade Task.

Single-unit (SU) activity-action potentials isolated from one neuron-has traditionally been employed to relate neuronal activity to behavior. However, recent investigations have shown that multiunit (MU) activity-ensemble neural activity recorded within the vicinity of one microelectrode-may also contain accurate estimations of task-related neural population dynamics. Here, using an established model-fitting approach, we compared the spatial codes of SU response fields with corresponding MU response fields recorded from the frontal eye fields (FEFs) in head-unrestrained monkeys (Macaca mulatta) during a memory-guided saccade task. Overall, both SU and MU populations showed a simple visuomotor transformation: the visual response coded target-in-eye coordinates, transitioning progressively during the delay toward a future gaze-in-eye code in the saccade motor response. However, the SU population showed additional secondary codes, including a predictive gaze code in the visual response and retention of a target code in the motor response. Further, when SUs were separated into regular/fast spiking neurons, these cell types showed different spatial code progressions during the late delay period, only converging toward gaze coding during the final saccade motor response. Finally, reconstructing MU populations (by summing SU data within the same sites) failed to replicate either the SU or MU pattern. These results confirm the theoretical and practical potential of MU activity recordings as a biomarker for fundamental sensorimotor transformations (e.g., target-to-gaze coding in the oculomotor system), while also highlighting the importance of SU activity for coding more subtle (e.g., predictive/memory) aspects of sensorimotor behavior.

Integration of landmark and saccade target signals in macaque frontal cortex visual responses.

Visual landmarks influence spatial cognition and behavior, but their influence on visual codes for action is poorly understood. Here, we test landmark influence on the visual response to saccade targets recorded from 312 frontal and 256 supplementary eye field neurons in rhesus macaques. Visual response fields are characterized by recording neural responses to various target-landmark combinations, and then we test against several candidate spatial models. Overall, frontal/supplementary eye fields response fields preferentially code either saccade targets (40%/40%) or landmarks (30%/4.5%) in gaze fixation-centered coordinates, but most cells show multiplexed target-landmark coding within intermediate reference frames (between fixation-centered and landmark-centered). Further, these coding schemes interact: neurons with near-equal target and landmark coding show the biggest shift from fixation-centered toward landmark-centered target coding. These data show that landmark information is preserved and influences target coding in prefrontal visual responses, likely to stabilize movement goals in the presence of noisy egocentric signals.

Integration of allocentric and egocentric visual information in a convolutional/multilayer perceptron network model of goal-directed gaze shifts.

Allocentric (landmark-centered) and egocentric (eye-centered) visual codes are fundamental for spatial cognition, navigation, and goal-directed movement. Neuroimaging and neurophysiology suggest these codes are initially segregated, but then reintegrated in frontal cortex for movement control. We created and validated a theoretical framework for this process using physiologically constrained inputs and outputs. To implement a general framework, we integrated a convolutional neural network (CNN) of the visual system with a multilayer perceptron (MLP) model of the sensorimotor transformation. The network was trained on a task where a landmark shifted relative to the saccade target. These visual parameters were input to the CNN, the CNN output and initial gaze position to the MLP, and a decoder transformed MLP output into saccade vectors. Decoded saccade output replicated idealized training sets with various allocentric weightings and actual monkey data where the landmark shift had a partial influence (R 2 = 0.8). Furthermore, MLP output units accurately simulated prefrontal response field shifts recorded from monkeys during the same paradigm. In summary, our model replicated both the general properties of the visuomotor transformations for gaze and specific experimental results obtained during allocentric-egocentric integration, suggesting it can provide a general framework for understanding these and other complex visuomotor behaviors.

Preattentive processing of visually guided self-motion in humans and monkeys.

The visually-based control of self-motion is a challenging task, requiring - if needed - immediate adjustments to keep on track. Accordingly, it would appear advantageous if the processing of self-motion direction (heading) was predictive, thereby accelerating the encoding of unexpected changes, and un-impaired by attentional load. We tested this hypothesis by recording EEG in humans and macaque monkeys with similar experimental protocols. Subjects viewed a random dot pattern simulating self-motion across a ground plane in an oddball EEG paradigm. Standard and deviant trials differed only in their simulated heading direction (forward-left vs. forward-right). Event-related potentials (ERPs) were compared in order to test for the occurrence of a visual mismatch negativity (vMMN), a component that reflects preattentive and likely also predictive processing of sensory stimuli. Analysis of the ERPs revealed signatures of a prediction mismatch for deviant stimuli in both humans and monkeys. In humans, a MMN was observed starting 110 ms after self-motion onset. In monkeys, peak response amplitudes following deviant stimuli were enhanced compared to the standard already 100 ms after self-motion onset. We consider our results strong evidence for a preattentive processing of visual self-motion information in humans and monkeys, allowing for ultrafast adjustments of their heading direction.

Multi-segment phase coupling to oscillatory visual drive.

BACKGROUND: It has been shown that humans adapt their postural sway to oscillatory, visually simulated self-motion. However, little is still known about the way individual body segments contribute to this adjustment of body sway and how this contribution varies with different environmental conditions. RESEARCH QUESTION: How do the centre of pressure (COP) and individual body segments phase-lock to a sinusoidal visual drive depending on the frequency of stimulation? METHODS: In this study, we introduce phase coupling as a method for assessing full body motion in response to visual stimuli presented in virtual reality (VR). 12 participants (mean age: 31 ±â€¯9 years) stood inside a virtual tunnel which oscillated sinusoidally in the anterior-posterior direction at a frequency of 0.2 Hz, 0.8 Hz or 1.2 Hz. Primary outcome measures were the trajectories of their COP as well as of 25 body segments obtained by a motion tracking system. RESULTS: Subjects significantly coupled the phase of their COP and body segments to the visual drive. Our analysis yielded significant phase coupling of the COP to the stimulus for all tested frequencies. The phase coupling of body segments revealed a shift in postural response as a function of frequency. At the low frequency of 0.2 Hz, we found strong and significant phase coupling homogeneously distributed across the body. At the higher frequencies of 0.8 Hz and 1.2 Hz, however, overall phase coupling became weaker and was centred around the lower torso and hip segments. SIGNIFICANCE: Information on how the visual percept of self-motion affects balance control is crucial for understanding visuomotor processing in health and disease. Our setup and methods constitute a reliable tool for assessing perturbed balance control, which can be utilized in future clinical trials.