Sensorimotor transformation is fundamental for survival. Neurons in many visuomotor structures in the oculomotor axis discharge an initial visual burst of activity to register the visual stimulus and later a motor burst to trigger a movement that redirects the visual axis to the object of interest. Given that such neurons project to the saccade generating circuitry in the brainstem, a long standing enigma of sensorimotor transformation is why the visual response is insufficient to trigger a movement while the second motor burst is. One leading theory states that the saccade is triggered when activity reaches a threshold. This view is unsatisfactory because the threshold level could be crossed by the visual burst also but without triggering a saccade. Another theory contends that movement onset occurs when variability in neural activity is reduced. Support for this hypothesis is based on variability measured across trials. This is not a feasible mechanism for neurons decoding their input spikes to decide when to trigger a saccade. Ideally, the decoding must be based on the structure of neural activity within a trial. We propose an innovative perspective - our central hypothesis - that saccade initiation occurs when an increase in firing rate is coupled with temporal stability in the population activity throughout the oculomotor neuraxis. More specifically, we suggest that the visual burst in all visuomotor elements is unstable and therefore cannot trigger a saccade, while the premotor burst is stable and initiates the movement when the firing rate crosses a threshold. Temporal stability is defined by a metric that tracks similarty or consistency as a function of time within a normalized neural trajectory defined by a population of neurons recorded either simultaneously or serially. Preliminary data from superior colliculus and frontal eye field neurons recorded sequentially during the delayed saccade task indicate that firing rate is unstable during the transient visual response but remains stable during the premotor burst that precedes saccade onset. We propose to address the following emerging questions using a combination of electrophysiological and computational approaches: What are the dynamics of temporal stability profile when visual and motor bursts overlap or merge, such as during reactive and express saccades, respectively? Does temporal stability exhibit similar properties when analyzed over many neurons recorded simultaneously? Do insights on neural variability obtained from across trials (e.g., Fano factor, optimal subspace) and within trials (temporal stability) analyses complement each other? How would temporal stability be implemented in a generic downstream neuron? How can this decoder algorithm be incorporated in a circuit-level model of saccade control?

Public Health Relevance

Patients suffering from neuropsychiatric disorders like schizophrenia, attention deficit hyperactivity disorder, and autism are often unable to time movements according to the criterion imposed of the behavioral task. We hypothesize that the temporal statistics of the neural activity during the sensory response is altered in such states. We propose to conduct electrophysiological experiments and develop a computational model to gain insights into how and whether temporal structure in population activity contributes to saccade initiation.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-Q (03)M)
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Araj, Houmam H
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University of Pittsburgh
Biomedical Engineering
Schools of Engineering
United States
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Smalianchuk, Ivan; Jagadisan, Uday K; Gandhi, Neeraj J (2018) Instantaneous Midbrain Control of Saccade Velocity. J Neurosci 38:10156-10167
Jagadisan, Uday K; Gandhi, Neeraj J (2017) Removal of inhibition uncovers latent movement potential during preparation. Elife 6:
Jagadisan, Uday K; Gandhi, Neeraj J (2016) Disruption of Fixation Reveals Latent Sensorimotor Processes in the Superior Colliculus. J Neurosci 36:6129-40