GAZZALEY, Adam  Top-down Modulation Deficit Cognitive Aging  UCSF May 17 2012

direc of Neurosci Imaging Center
of Depts of Neurology, Physiology, and Psychiatry  UCSF  (at Mission Bay in SF)

title of talk:  Top-down modulation deficit as an underlying mechanism of cognitive aging.

pron  GAZZ uh lee.

worked with Bob Knight and with Mark D'Esposito at Cal, Berk.

what underlies the changes in the healthy older brain that underlie changes in cognition.

he is an MD, PhD.

sl = slide
shows  an older man looking into a frige who does not remember  what he's looking for
or why he's there... a "senior moment"

our population is aging...  2011... baby boomers are age 65.

goal:  identify alterations in brain function that underlie changes in cognition

his lab does  fMRI,  EEG,  and TMS = transcran mag stim.

working at the  crossroads of attention = attn   and memory = mem

Samuel Johnson  1759:  the true art of memory is the art of attention

... a man ...must be able to evacuate his mind
if the mind is full, what can it receive?...  etc.

Cognitive Control

Perception...   there is external, stimulus-driven attn... bottom-up attn (eg the ventral visual pathway) and

also  top-down... choosing what you attend to. (PFC = prefrontal cortex)

wm = working memory   vs  LT mem = long-term mem.

FOCUS.... focusing  vs ignoring...

the two faces of top-down attention

are  Ignoring  and Focusing  separate  or do they overlap...?
(his view is that ignoring  (ie suppressing extraneous input is an active process and
when it is disturbed, it erodes working mem)

projection from  PFC and parietal cortex that provide  top-down modulation  of  (eg  IT = infer temp cortex)
vs  bottom-up processing  (eg, the ventral visual pathway)

he will discuss two forms of modulation:
Stimulus--present modulation  (with actual stim)  vs

Stim-absent modulation  eg
with mental imagery,  working memory maint.,  LT memory recall,  expectation..
(planning for an event that has not yet occurred)

study  1:
younger partic  are ages 18 to 30... students
vs older pts  ages 60 to80  ... v healthy older folks on
no meds, no depression and no dementia
(all are healthy adults with no known plaques etc)

Interference  (his theory / model of what's going on)
put together model and then try to test model with studies...

Distractors can be either internal or external...

External  eg distraction  vs
interruptions  (multi-tasking)

Internal
eg  intrusions (mind wandering)
vs  diversions  (multi-tasking)

(think of PTSD and OCD...  sources of  internal distractions)

***
study 1  (at Bob K and Mark D's lab)  ... his first study

hold probe in mind  does it match  initial cue

eg  remember  scenes and ignore faces  and then  say match or not  to a probe  after a 9 sec delay... show probe for 2 secs.

then switch... remember faces and ignores scenes....

see Gazz  Nat Neurosci  2005
and J of Cog Neurosci in 2005....

suppression (ie ignoring scenes) is not a passive process... it's an active process...

remember faces  while ignoring scenes.

his first big finding in cog neurosci... a problem with  the act of ignoring...
older pts had trouble ignoring the interfering stim  (supression is an active process)

there is a correl. btwn how well you ignore irrelevant and how well you recall  relevant info...

the older pts  COULD actually remember the interfering stim...

look at very early  evoked potential  N170  (negative swing at 170 ms) suppression index...

older  pts  have lost the ability to RAPIDLY suppress irrelevant info.
(must rapidly suppress distractor, otherwise it will interfere.)

*****
interim summary...

the suppression deficit:
is assoc with WM impairment
also occurs in younger adults...
preparation does NOT help this  (even with pts who KNOW what is irrel  etc.  does not matter)
this occurs only in early stage of visual processing  (within the first 200 ms)
you can practice this and get somewhat better with limited prac (1 hour) but stilll persists.
is assoc with changes in prefrontal-visual cortical func connectivity...
(that study is in review)

so,  that's  DISTRACTION...  it has a negative impact on performance...

****
*****
on to  Interruptions  INTERRUPTIONS...
(various kinds of interruptions)
this can even be shown with younger partic...

(interruptions are where you actually must DO something over and above being distracted from initial stim)

but  big effect with age...
the interrup effect is even bigger than the distraction effect..
what's going on?

eg look at N170 index...

the more they process the interrupting stim  the worse they do...
ie  deviation from the primary task  is bad..

BUT  different mechs apparently btwn  distractors and interruptors...

What is the neural basis of the greater impact of interruption in aging?

PPA =  parahippocampal place area  (scene area)

look at func connectivity bgtwn MFG and PPA
mfg = middle frontal gyrus...

need to maintain the task thru the distractions...

must maintain the repres thru distractions... on the other hand  interruptions require REACTIVATION. . 

the older adults could NOT  reactivate the repres

see Clapp, Rubens  et al  in  PNAS 2010 and 2011..

older adults  cannot disengage the interrupter  (he refers to  it as the STICKINESS of the interrupter)
a disengagement problem  (each event that you interact with  sucks you in for  a few seconds... you cannot disengage)

is it simply that the kids are  training on facebook etc.  and that accounts for the diff... (btwn the students and the older adults)

how abt monkeys... eg  Carol Barnes  work...

do this in macaques....  try and do same expts in monkeys  (with trodes in pfc and visual areas)

this same effect may occur no matter what you are doing...

*****
*****

Stimulus Absent
Top-down Modulation

will now show same thing with LT mem recall  (eg  1 hour)

in this study

S  saw  168  novel images...  crowns,   couches, vacuum cleaners, etc...

one hour later... hear crown  and press 3  (cuz there were 3 crowns on the card that they saw)
100% of S  use  mental imagery...

see Wais  J Neurosci  in 2010...

was this simply due to  visual distraction  (trying to sketch on a dirty sketchpad)
but  to test that...
also used auditory  distractor... same result
so... NOT due to  mode of pres..
rather its due to  operation of network..  left HC and left IFG...

older pts  have larger distraction index...

*****
MENTAL IMAGERY

Kalkstein  Jneurosci in 2011    used TMS  to get at causality...
mental imaging and aging...

so, first look at brains during viewing  (fMRI)

compare  faces to motion  (flow field)
no age differences  btwn younger and older...

you do use the same areas for imagery as you do for de novo visualizaiton...

but  relative  inability  to selectively  map to  network in older adults...

*******
EXPECTATION  (when preparing for a task)

two tasks  just remember face  OR
remember whether scene or face

see bollinger citation.

during the expectation period,  younger adults are better at
modulating the network to prepare it for stimulus...
all abt top-down control...
premodulate an area that then benefits memory....

Gazz  Prin of Frontal Lobe Function 2011... a chapter in a book that will be coming out  (he wrote a review)

related to alterations in prefrontal sensory cortical networks...

there are no long range GABAergic networks... they're all  excitatory....
(so how does suppression work?)

****
he shows  final... big improvement in older adults  playing a driving video game with massive improvement following practice...

dorsal attn network...  medial pfc.