KRAUZLIS Rich Subcortical Control of Eye Movements NIH Nov 8 2012

he's at National Eye Instit; NIH;

email is richard.krauzlis@nih.gov

Lab of Sensorimotor research.

Ryan Squire does intro  (he is in Tirin Moore's Lab)

undergrd at Princeton  then
PhD student with Lisberger at UCSF

did work in cerebellum;

1997 at SALK Instit  set up...
last year... moved back to NIH  Section Chief there;

reversible lesion in monkeys;  pharmocologic  inactivation
last 3 years... 6 separ papers using inactivation techniques  (v  productive)

title is  SUBCORTICAL CONTROL of SPATIAL ATTENTION

this will be SC = superior colliculus work...

what is spatial attention...

based on Rensink 1997;

slide 1  an example of spatial attention:  change blindness...

u have an experience that u r taking it all in..

but in fact u  just register. a small subset...(of what's out there)

interposed with gray screen...  change blindness...  a light is changing from red to green...

Spatial attention and biased competition

visual inputs  come in and there is competition for repres in visual cortex
there are priority signals that determine what you actually see

(biased competition)

he shows paths in Rhesus monkey brain...

biasing signals come from LIP and FEF and DLPFC....

the seeing takes place in areas like V1 V4 and MT...

but lots of  subcortical regions involved also

he shows  8 or so areas...

SC is v important = superior colliculus...

iconic image of  sup collic...

oculocentric map...

he shows L  super collic...

u evoke saccadic eye mvmts if you stim SC...  retinotopic map for saccades...

but if u dial down the current  (do not get saccade but get...  attention like shift in performance  (ie get biasing)

slide:  SC and ATTN...  do weak elec stim...

goes to  infer pulvinar  to either MT or  V3

or from SC to  thalmus to  LIP

another path goes from SC to ? thalamus  to V1 or V3...

we did...  chemical inactivaiton  to  inactivate SC  block it...

cause a severe behavioral  impairment

Lee Lovejoy did this work  md, phd student  in nature neurosci in 2010

the task...  fixate;  in center;  one ring is colored  eg

4 sqare with one  one red ring  for 480 ms;

then shows random dot  inside eg red ring...

then rings disappear....

then  for 480 to 4000 ms  just randoms dots

then  160 ms  ....

an example trial

fixate the spot..

dots going up and to the right...

correct  means u saccade in cued signal direction  
error if u  choose foil signal direciton

error choose neither signal direciton

monkey  does this corect 70% of time;
mistakenly uses the foil 20% of time;   other directions  5% of time

(4 possibs....  eg  down and to the R  is correct;  up to the R cued by foil)  etc)

injectrode....  use muscimol... which is a gaba A  agonist)

latencies of vis guided saccades  demonstrate the extent of inactivated region...

we oriented the bevel to direct the direction of infusion in that direction...

aim it in the target direciton...

it has  incr  saccad  latency...

so, what happens when the cued stim is placed int he inactivated region...

[re-inactivation...  83%  is correct and 17%   are cued by foil)

post-injection;

now 78% go to foil motion and only 22% go in the cued direciton...

there is a complementary flip...

hugely signif effect... v robust effect... v large impairments...

is there motor impairment?  prob not...
 we throw out the trials where there is motor impairment..

****
now do same trials witn hand... press buttons with their hand...

even with manual responses... get exactly the same effect... (so it is not  a motor prob)

***
is it simply difficult to SEE the patch in the affected rgion?

do another type of control...

mapped  psychometric function...

Y axis is on probit scale...
 how much do I have to change the signal to get  reduction in sensitivity to motion

result:  inactivation does causes a SMALL but signif reduction in sens to motion...

so, there is a small  effect...

so,  compensate  for this small sensory impairment by augmenting the signal in the affected region...

but even with augmented  signal at the cued location does NOT rescue the impairment due to mucinol...
ie  he still errs  in direction of  foil.

SUMMARY:

so  SC activity is necessary for the normal control of visual spatial attention...

so, what happens to attn-related  ....

work done by Alex Zenon...

classic work was done by  true and mansell in 96 and 99...

job of animal is to detect a change of dot motion at the cued location but NOT at the foil location

monkey's response is to press the button...

muscmol  0.25 to 0.5 microliter...

hit rate changes from  80% to  20%...  (no motor impairment)

Zenon and krauzlis  2012 in nature...

what happens to firing rate in middle superior temp area...

he shows  cued vs  not cued... u see big  gain modulation  due to cueing

modulation index = 0.28...

BUT...  modulation index is NOT changed! 
 (despite the fact  that  animal's  behavior has gone from 80% accuracy to 20% accuracy)

this is  recording from MST

so  no  change in gain modulation  from pre to post  in either MST or in MT....

but  attention not only changes firing rate, but also the variability in firing rate.

use ROC  ... look at  area under ROC....

look at Fano Factor index...  variability across trials...

variability is  decr with  spatial cuing  (but unchanged  from pre to post injection)

what happens to inter-neuronal correlations during SC inactivation...

but again... no change in either  MT or MST...

so lots of other controls  that show no change...

So,  what happens to attention-related effects in extrastriate cortex after SC inactivation?

conclusion

1) SC is nec for normal control of spatial attentiol  BUT
2)  SC acts through mechanisms DIFFERENT from
 the well known signatures of attn in extrastriate cortex...

Speculation:

The SC  provides a spatial INDEX that regulates  which visual signals are used,
 but does not alter how those signals are represetned.

eg  what goes into memory...
so where wud that take place?

which neuronal circuits work with the SC to control spatial atteniton

perhaps  its  FEF   (SC  goes to  med dorsalis then to FEF

***
another possib...

perhaps  thru effect in caudate nucleas  (via  centromedian  nucleus in thalamus)

also another  path to pontine nuclei to cerebellum...

so,  many anatom candidates...

presumabldy lots of these mechs are conserved phylogenetically...
underscores importance of looking at birds, etc.

Bill Newsome:  the readout seems to be impaired
A:  there are dissociable effects..
BN  response;  how abt  putting muscimol in FEF?

A   another possib... anatom  locus  may not be  in visual system at all...
might be in a multimodal area...

may be  using an area that  this is involved in spatial alloc  but is not part of visual system...

Jon W:  is there facilitation in direction of foil?