A neural test bed for simulating executive control deficits in saccade generation

Uday JagadisanNeeraj GandhiUniversity 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)

C

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 500-1200 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

caudal

rostral

SC

Experimental Methods

TIME (ms)

Target

Fixation Point

Eye

Air-puffEye lid

Single units in rostral and caudal SC (intermediate layers) of monkey (macaca mulatta)

Delayed saccade (overlap 500-1200 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

TIME (ms)

Target

Fixation Point

Eye

Air-puffEye lid

For more on these trials, please visit my poster on Monday afternoon (QQ13 489.01)

Activity in the rostral SC – control vs fixation blink

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Time from blink onset (ms)

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ControlFixation Blink

5 deg

-400 -200 0Time from saccade onset (ms)

Start of blink

End of blink

n = 449Suppression lasts past the blink into the delay period …

… even as the eyes are stable.

Activity in the rostral SC – Summary (4 neurons)

Significant

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1 2 3 4Cell Number

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Delayperiod During saccade

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p < 0.0001 p > 0.05ControlFixation Blink

C

Activity in the rostral SC – Summary (4 neurons)

Significant

1 2 3 40

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1 2 3 4Cell Number

Activ

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Delayperiod During saccade

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p < 0.0001 p > 0.05ControlFixation Blink

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n = 440n = 75

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Increased activity in the visual response

Activity in the caudal SC – visual and delay activity

Activity in the caudal SC – visual and delay activity Control

Fixation Blinkn = 540n = 73

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ControlFixation Blink

n = 440n = 75

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ControlFixation Blink

n = 168n = 42

Time from target onset (ms)

Activ

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Activ

ity (s

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ControlFixation Blink

n = 307n = 7

Time from tar

Periods of increased activity

Activity in the caudal SC – saccade-related burst

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n = 540n = 73

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n = 440n = 75

Time from saccade onset (ms)

Activ

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n = 307n = 7

Time from saccade onset (ms)

Activ

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n = 168n = 42

Time from saccade onset (ms)

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ity (s

pi

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

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Activity incontrol trials

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Activity incontrol trials

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Activity incontrol trials

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Activity incontrol trials

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

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Propo

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n eac

h bin

Time from GO cue (ms)

ControlFixation blink -correctFixation blink - early

0

Behaviour – early (delay period) saccades

Story so far ...

What happens on these trials?

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ControlFixation Blink - correct

Increased excitability associated with early saccades

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ControlFixation Blink -correctFixation Blink - early

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ControlFixation Blink - correctFixation Blink - early

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

Lab Support Neeraj Gandhi Husam Katnani NIH Grant

EY015485 Gloria Foster Joe McFerron

Thank you!

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ControlFixation Blink -correctFixation Blink - earlyGapTask

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Activity during “early” saccades

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ControlFixation Blink

Tar

Increased activity in SC location opposite to target