The oculomotor repertoire is governed by alternating activity patterns in competing networks that generate saccades and preserve fixation. When the operation between the two networks is properly maintained, eye movement function is normal. A bias in the balance of activity, however, can lead to dysfunction. For example, decreasing the efficacy of the fixation network or enhancing the activity of the saccade generation network compromises the ability to delay or inhibit movements. This proposal seeks to examine the activity of neural elements in these networks and the consequence on behavior during a perturbation that alters the balance between the two. The focus is specifically on the superior colliculus, whose rostral pole is involved in preserving fixation and caudal region is essential fo generating saccades. The perturbation of choice is to induce a blink by delivering an air-puff to an eye as subjects perform various oculomotor tasks. Blinks have been shown to compromise the integrity of the saccadic inhibition network at the level of the pons, and if the blink is triggered after presentation of the saccade target (and permission to initiate the movement), the goal-directed movement accompanies the blink at a reduced latency.
Specific Aim 1 examines the effects of a blink on the fixation and saccade generation networks in the superior colliculus. It specifically tests the hypothesis that blinks suppress activity in the fixation network (rostral region) and increases the excitability of the saccade generation network (caudal region).
Specific Aim 2 examines whether the underlying neural activity at the time of prematurely triggered saccades encodes premotor information. It will specifically test the threshold principle of the motor preparation hypothesis and whether spatial attention and motor preparation can be dissociated. We anticipate that the combination of behavioral and neurophysiological approaches will provide insights into neural mechanisms that are altered in neuropsychiatric disorders (e.g., ADHD, schizophrenia) characterized by an inability to suppress reflexive movements.

Public Health Relevance

A common symptom associated with neurological conditions like schizophrenia, attention deficit hyperactivity disorder and autism is the inability to refrain from either initiating the motor preparation process or triggering the developing motor plan. Our objective is to use a behavioral perturbation to simulate deficits in saccade planning/initiation i healthy subjects. Combining this approach with neural recordings will also yield insights into neural mechanisms of motor preparation and saccade initiation in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
4R01EY022854-04
Application #
9053491
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Araj, Houmam H
Project Start
2013-05-01
Project End
2017-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Smalianchuk, Ivan; Jagadisan, Uday K; Gandhi, Neeraj J (2018) Instantaneous Midbrain Control of Saccade Velocity. J Neurosci 38:10156-10167
Goffart, Laurent; Cecala, Aaron L; Gandhi, Neeraj J (2017) The superior colliculus and the steering of saccades toward a moving visual target. J Neurophysiol 118:2890-2901
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
Cecala, Aaron L; Smalianchuk, Ivan; Khanna, Sanjeev B et al. (2015) Context cue-dependent saccadic adaptation in rhesus macaques cannot be elicited using color. J Neurophysiol 114:570-84
Katnani, Husam A; Gandhi, Neeraj J (2013) Time course of motor preparation during visual search with flexible stimulus-response association. J Neurosci 33:10057-65