Nicholas Seow Chiang Price

During smooth pursuit eye movements, the visual system must compensate for self-generated retinal motion to achieve stable perception of motion in the environment. This compensation primarily depends on an efferent copy of motor commands. Systematically under- or overweighting the strength of efference copy should lead to correlations between eye movement velocity and perceived object velocity. However, previous examinations of these trial-by-trial perceptual correlations have produced mixed results. It remains unclear how effectively the brain compensates for eye movement induced retinal motion during pursuit, and what this reveals about the way efference copy influences perception. To address this, we developed a speed perturbation paradigm in which 29 participants tracked a moving target that underwent brief speed changes. On each trial, we recorded eye velocity along with perceptual judgments of the sign of the speed change (faster or slower) and confidence ratings for those judgments. Across participants, perceptual and oculomotor sensitivity were correlated (r = 0.53), but trial-by-trial perceptual and oculomotor responses appeared independent. A logistic regression model incorporating efference copy gain to predict perceptual reports from stimulus speed and eye speed revealed systematic under-compensation for eye movements; faster eye movements were associated with lower changes in perceived speed. Confidence ratings were well-calibrated to perceptual accuracy and showed a consistent negative relationship with eye movement speed. Collectively, these results are consistent with systematic undercompensation for eye movements through the use of efference copy during motion perception.

The Box and Block Test (BBT) is a clinical assessment of gross manual dexterity, requiring participants to move small blocks between two boxes. It is scored using the number of blocks transferred in 60 s; a high score requires rapid arm movements and accurate grasping, with no constraints on block placement accuracy. A low score cannot distinguish inaccurate movements from slow movements. To address this, we explored two variations of the standard BBT using 16 blocks moved in a predefined sequence. The insert BBT requires inserting blocks into recesses that constrain accuracy. The targeted BBT requires placing each block onto a target, allowing measurement of movement timing and accuracy. Across participants, movement times for the insert and targeted BBT were strongly correlated, but only weakly correlated with the standard BBT scores. Two speed-accuracy tradeoffs were evident: within participants, slower placements were generally more accurate; and across participants, those who moved more slowly were generally more accurate. Surprisingly, locations associated with faster movements were also associated with more accurate block placements, highlighting the spatial affordances of the block locations. Our tasks capture performance features absent in the standard BBT and emphasize the value of designing dexterity tasks that evaluate both speed and accuracy.

A new electrical stimulation focused computational model of the visual cortex had been created to aid in the development of cortical visual prosthesis. The model consists of 10,666 biophysical neurons representing 0.13mm ³ of a layer 2/3 of the primary visual cortex and was calibrated to match the baseline activity of rat brain recordings. A novel model of electrical stimulation was developed to allow for selective activation of specific neuron types, and matched the single cell stimulation response generated by known stimulation models. The electrode was tuned to match recorded population level change in activity across distances and currents recorded in the rat’s brain. The model is now ready to explore electrical stimulation effects on the visual cortex for examination of neuron specific stimulation to assist in the development of cortical visual prosthesis.

Objective: Intracortical electrical stimulation is used to modulate brain activity. However, non-selective neuronal activation limits its efficacy. A biphasic electrical stimulation pulse has cathodic (negative) and anodic (positive) phases; swapping them changes current direction. In computational models, different current directions selectively recruit distinct neuronal populations. Whether this occurs in intracortical stimulation is unknown. We tested whether current direction affects the recruitment of neuronal populations in vivo, and by what mechanism. Approach: We implanted 20 anaesthetized rats with multichannel silicon probes in the visual cortex to simultaneously stimulate and record across all cortical layers. Stimulation used either cathodic-first or anodic-first biphasic pulses. Models also predict that current direction effects strengthen when the second phase is lengthened relative to the first; therefore, in 7 animals, we tested scaled pulses. Results: Cathodic-first pulses evoked stronger responses than anodic-first pulses in input and deep layers. Extending the pulse's second phase transformed cathodic-first magnitude advantage into selective recruitment by collapsing anodic-first neuronal response. This anodic-first deficit was layer- and orientation-dependent. Namely, anodic-first activation spread was weakened specifically in input and deep layers in the horizontal dimension, but not superficially. Conclusion: Although cathodic-first pulses are generally more effective, this advantage is not uniform across cortical depth, indicating current direction-dependent spatial selectivity. This selectivity is consistent with layer-specific fiber architecture: horizontally-passing fibers, more easily activated by cathodic-first pulses, dominate in the input and deep layers, while radial fibers - superficially. Therefore, current direction can be used as a stimulation parameter in cortical prostheses to achieve layer- and orientation-dependent spatial selectivity.

Objective: Intracortical electrical stimulation is used to modulate brain activity. However, non-selective neuronal activation limits its efficacy. An electrical stimulation pulse has cathodic (negative) and anodic (positive) phases; swapping them changes current direction. In computational models, current direction preferentially recruits distinct neuronal populations. Whether this also occurs in intracortical stimulation is unknown. We tested whether current direction selectively activates neuronal populations in vivo, and by what mechanism. Approach: We implanted 20 anaesthetized rats with multichannel silicon probes in the visual cortex to simultaneously stimulate and record across all cortical layers. Stimulation used either cathodic-first or anodic-first biphasic pulses. Models also predict that current direction effects strengthen when the second phase is lengthened relative to the first; in 7 animals, we, therefore, tested scaled pulses. Results: Cathodic-first pulses activated twice as many cortical sites as anodic-first. Cathodic-leading stimulation evoked greater firing rates in input and deep layers, while superficial layers responded comparably to both. Reducing second-phase amplitude, while keeping total charge constant, selectively attenuated anodic-first responses in input and deep layers, sparing superficial layers. Cathodic-first scaled pulses produced greater horizontal spread in input and deep layers, but not superficial. Conclusion: Current direction recruits overlapping but distinct neuronal populations, depending on the cortical layer. In input and deep layers, cathodic-first pulses dominated, likely because these layers are rich in horizontally passing fibers. Superficially, where neurons are oriented more radially to the electrode, this advantage disappeared. This layer-dependent geometry links our in vivo findings to model predictions of how current direction shapes neuronal recruitment.

Motor outputs vary even in response to identical sensory inputs, yet the origin of this variability within the sensorimotor pathway remains unresolved. Here, we evaluate how variability in sensory representations can explain behavioural fluctuations in a reflexive oculomotor task. We used Neuropixels probes to record neuronal activity in area MT of marmosets during ocular following responses and applied partial least squares regression to extract the shared variance between population activity and eye movements. Stimulus-evoked activity reliably predicted trial-by-trial variability in open-loop eye velocity. Additionally, closed-loop analyses revealed trial-by-trial correspondence between eye movements and subsequent neural responses. These results demonstrate that variability in sensory neural populations contributes to motor variability, supporting the claim that sensory noise is propagated through the sensorimotor pathway. Surprisingly, however, traditional models trained to only capture neural variability across trials poorly predicted behavioural variations, suggesting that only a subset of sensory representations is accessible to the motor system.

Despite the widespread application of general anesthesia since the 19th century, a fundamental understanding of its operating principle and a reliable metric of consciousness remains elusive. We here analyze Loss of Responsiveness (LoR) induced by propofol anesthesia in humans and macaque monkeys. Through application of “highly comparable time series analysis” (hctsa) over 7000 features, we aim to identify LoR metrics common to both humans and macaque monkeys. In Stage 1 analysis, we trained a nearest median classifier using 200 ms data epochs using one macaque individual, and evaluated its classification accuracy on human intracranial data, recorded from one participant. This analysis suggested the existence of univariate features capable of discriminating between awake and propofol-induced unresponsive states in both species. Stage 2 extended the analysis to additional macaque and human recordings to evaluate cross-session and cross-species generalization. We identified many hctsa features that commonly distinguished awake from unresponsive states across sessions and species, in the frontal, but not in parietal and temporal, recordings. In exploratory analyses, we aimed to distinguish loss of responsiveness from consciousness, by additionally analyzing human data under sedated yet conscious state in a within-subject manner. This analysis revealed that frontal, temporal and parietal recordings contain similarly sensitive features and channels as signatures of consciousness. These results support the existence of ECoG time-series features associated with propofol-induced loss of responsiveness across humans and macaques, while also highlighting the challenge to determine whether such features specifically track conscious experience rather than responsiveness.