A neural test bed for simulating executive control deficits in saccade generation Uday Jagadisan Neeraj Gandhi University of Pittsburgh

Typical oculomotor behaviour displays an alternating pattern of gaze shifts and fixations Balanced exchange of activity in the brain between inhibitory networks that maintain fixation and excitatory networks that generate gaze shifts Balance shift towards increased inhibition  difficulty or delay in initiating movements Balance shift towards increased excitation  lack of movement suppression (behaviour as seen in disorders such as ADHD, Schizophrenia) Sensorimotor function – a balance hypothesis

Model - Reciprocal inhibition in the superior colliculus (SC) (illustration from Munoz & Fecteau, 2002)

Biasing the rostro-caudal balance in SC Objective: Perturb the balance between rostral SC and caudal SC on a trial-by-trial basis while recording activity in both networks  cannot use microstimulation (difficult to stimulate and record in the same place)  cannot use inactivation (recovery over long time-scales) Can we use the blink reflex to our advantage? Omnipause neurons (OPNs) in the PPRF have been shown to shut off during blinks, linked to loopy eye movement associated with blink Like the OPNs, cells in the rostral SC show a reduction in activity related to saccades – can they also be turned off using blinks? If so, what are the consequences of this on the caudal network? Schultz, et al. (2010)

Single units in rostral and caudal SC (intermediate layers) of monkey (macaca mulatta) Delayed saccade (overlap  ms) paradigm Air-puff delivered at random time on ~25% of trials; analysis focuses on blinks during initial fixation (Fixation Blinks) Saccade target – IN or OUT of response field Experimental Methods

Single units in rostral and caudal SC (intermediate layers) of monkey (macaca mulatta) Delayed saccade (overlap  ms) paradigm Air-puff delivered at random time on ~25% of trials; analysis focuses on blinks during initial fixation (Fixation Blinks) Saccade target – IN or OUT of response field Experimental Methods For more on these trials, please visit my poster on Monday afternoon (QQ )

Activity in the rostral SC – control vs fixation blink Suppression lasts past the blink into the delay period … … even as the eyes are stable.

Activity in the rostral SC – Summary ( 4 neurons ) Significant

Activity in the rostral SC – Summary ( 4 neurons ) Significant

Increased activity in the visual response Activity in the caudal SC – visual and delay activity

Periods of increased activity

Activity in the caudal SC – saccade-related burst

Activity in the caudal SC – Summary ( 17 neurons, 2 monkeys )

Behaviour – early (delay period) saccades Story so far... What happens on these trials?

Increased excitability associated with early saccades

Blinks during fixation lead to reduced fixation network activity that persists for several hundred milliseconds even as the eye position is stable The reduction of fixation network activity in the rostral SC may be related to the increased excitability in the response of neurons in caudal SC We have established a model that can be used to study the balance between excitation and inhibition in the saccadic system Summary

Acknowledgements Thanks to LabSupport Neeraj Gandhi Husam Katnani NIH Grant EY Gloria Foster Joe McFerron

Thank you!

Activity during “early” saccades

Increased activity in SC location opposite to target